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32 results on '"Olivier Disson"'

1. Innate immune responses to Listeria in vivo

Author

Sylvain Levallois, Olivier Disson, Claire Maudet, Marc Lecuit, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Paris (UP), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Research in the Biology of Infection Unit is supported financially by Institut Pasteur, Inserm, ANR and ERC, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
Microbiology (medical), [SDV]Life Sciences [q-bio], Placenta, Biology, medicine.disease_cause, Microbiology, 03 medical and health sciences, Listeria monocytogenes, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pregnancy, In vivo, medicine, Humans, Listeriosis, Pathogen, 030304 developmental biology, 0303 health sciences, Innate immune system, 030306 microbiology, medicine.disease, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immunity, Innate, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Blood-Brain Barrier, Bacteremia, Host-Pathogen Interactions, Immunology, Listeria, Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Listeria monocytogenes (Lm) is a foodborne bacterial pathogen that causes listeriosis, a severe infection that manifests as bacteremia and meningo-encephalitis mostly in immunocompromised individuals, and maternal-fetal infection. A critical pathogenic determinant of Lm relies on its ability to actively cross the intestinal barrier, disseminate systemically and cross the blood-brain and placental barriers. Here we illustrate how Lm both evades innate immunity, favoring its dissemination in host tissues, and triggers innate immune defenses that participate to its control.

Published
2021

2. Live Imaging Reveals Listeria Hijacking of E-Cadherin Recycling as It Crosses the Intestinal Barrier

Author

Cindy Fevre, Marc Lecuit, Minhee Kim, Olivier Disson, Morgane Lavina, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Minhee Kim received a long-term postdoctoral fellowship from the European Molecular Biology Organization (EMBO), ALTF 1192-2017. Institut Pasteur, Inserm, LabEx IBEID, the European Research Council (ERC) Invadis and ANR Organolist provided financial support., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-15-CE15-0007,OrganoList,Interactions entre Listeria monocytogenes et la barrière intestinale(2015), European Project: 681829,ERC-CoG-2015,INVADIS(2016), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, E-cadherin recycling, Listeria, [SDV]Life Sciences [q-bio], Vacuole, Biology, Endocytosis, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Bacterial Proteins, Listeria monocytogenes, Live cell imaging, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, Listeriosis, Internalin, intestine, organoids, Goblet cell, goblet cell, live imaging, Cadherins, Intestinal epithelium, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Cell biology, 030104 developmental biology, medicine.anatomical_structure, Transcytosis, Rab11, epithelial translocation, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Listeria monocytogenes is a foodborne bacterial pathogen that causes human listeriosis, a severe systemic infection [1]. Its translocation across the intestinal epithelium is mediated by the interaction of internalin (InlA), a Listeria surface protein, with its host species-specific receptor E-cadherin (Ecad) [2-5]. It occurs through goblet cells, on which Ecad is luminally accessible [6], via an unknown mechanism. In the absence of cell lines recapitulating this phenotype in vitro, we developed an ex vivo experimental system, based on the intraluminal microinjection of Listeria in untreated, pharmacologically-treated and genetically modified intestinal organoids. Using both live light sheet microscopy and confocal imaging, we show that Listeria translocates through goblet cells within a membrane vacuole in an InlA-and microtubule-dependent manner. As Ecad undergoes constant apical-basal recycling [7, 8], we hypothesized that Lm may transit through goblet cells by hijacking Ecad recycling pathway. Indeed, Listeria is stuck at goblet cell apex when Ecad endocytosis is blocked, and remains trapped intracellularly at the basolateral pole of goblet cells when Rab11-dependent Ecad recycling is compromised. Together, these results show that Listeria, upon docking onto its luminally accessible receptor Ecad, hijacks its recycling pathway to be transferred by transcytosis across goblet cells. Live imaging of host-pathogen interactions in organoids is a promising approach to dissect their underlying cell and molecular biology.

Published
2021

3. Making Sense of the Biodiversity and Virulence of Listeria monocytogenes

Author

Olivier Disson, Alexandra Moura, Marc Lecuit, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Research in the Biology of Infection Unit is supported financially by Institut Pasteur, Inserm, ANR and ERC. Marc Lecuit is a senior member of Institut Universitaire de France., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), DIAKITE, andrée, and Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID

Subjects
Microbiology (medical), [SDV]Life Sciences [q-bio], Biodiversity, Virulence, Genomics, adaptation, Biology, medicine.disease_cause, Microbiology, 03 medical and health sciences, Listeria monocytogenes, listeriosis, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, medicine, Animals, Humans, 030304 developmental biology, biodiversity, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 030306 microbiology, Intracellular parasite, Meningoencephalitis, medicine.disease, biology.organism_classification, Adaptation, Physiological, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, [SDV] Life Sciences [q-bio], virulence, Infectious Diseases, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Adaptation, Bacteria, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Listeria monocytogenes is a foodborne pathogen responsible for listeriosis, an infection that can manifest in humans as bacteremia, meningoencephalitis in immunocompromised patients and the elderly, and fetal-placental infection in pregnant women. Reference strains from this facultative intracellular bacterium have been instrumental in the investigation of basic mechanisms in microbiology, immunology, and cell biology. The integration of bacterial population genomics with environmental, epidemiological, and clinical data allowed the uncovering of new factors involved in the virulence of L. monocytogenes and its adaptation to different environments. This review illustrates how these investigations have led to a better understanding of the bacterium’s virulence and the driving forces that shaped it.

Published
2021
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4. Bacterial inhibition of CD8+T-cells mediated cell death promotes neuroinvasion and within-host persistence

Author

Lei Huang, Claire Maudet, Charlotte Gaultier, Marc Lecuit, Sylvain Levallois, Yu-Huan Tsai, Julien Gaillard, Marouane Kheloufi, Olivier Disson, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Cité (UPCité), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Work in ML laboratory is funded by Institut Pasteur, Inserm, ERC, ANR and Labex IBEID (ANR-10-LABX-62-IBEID). CM was a recipient of the Roux-Cantarini fellowship of Institut Pasteur. LH, CG and JG were supported by Université Paris Descartes, YHT by the Pasteur -Paris University (PPU) International PhD Program, under the European Union's Horizon 2020 research and innovation program, Marie Sklodowska-Curie grant agreement No 665807, and SL by FRM (ECO201906009119) and 'Ecole Doctorale FIRE–Programme Bettencourt'., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Paris (UP), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), DIAKITE, andrée, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Institut Pasteur International Docotal Program - PASTEURDOC - - H20202015-10-01 - 2020-10-01 - 665807 - VALID

Subjects
0303 health sciences, Programmed cell death, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 030306 microbiology, [SDV]Life Sciences [q-bio], Virulence, Biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Microbiology, [SDV] Life Sciences [q-bio], 03 medical and health sciences, Immune system, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunity, Humanized mouse, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cytotoxic T cell, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Pathogen, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, CD8, 030304 developmental biology
Abstract

Central nervous system infections are amongst the most severe1,2, yet the mechanisms by which pathogens access the brain remain poorly understood. The model microorganismListeria monocytogenes (Lm)is a major foodborne pathogen that causes neurolisteriosis, one of the deadliest central nervous system infections3,4. While immunosuppression is a well-established host risk factor for neurolisteriosis3,5, little is known regarding the bacterial factors underlyingLmneuroinvasion. We have developed a clinically-relevant experimental model of neurolisteriosis, using hypervirulent neuroinvasive strains6inoculated in a humanized mouse model of infection7, and we show that the bacterial protein InlB protects infected monocytes from CD8+T-cells Fas-mediated cell death, in a c-Met/PI3-kinase/FLIP-dependent manner. This blockade of anti-Lmspecific cellular immune response lengthens infected monocytes lifespan, favoringLmtransfer from infected monocytes to the brain. The intracellular niche created by InlB-mediated cell-autonomous immunosuppression also promotesLmfecal shedding, accounting for its selection as aLmcore virulence gene. Here, we have uncovered an unanticipated specific mechanism by which a bacterial pathogen confers to the cells it infects an increased lifespan by rendering them resistant to cell-mediated immunity. This promotesLmwithin-host persistence and dissemination to the central nervous system, and transmission.

Published
2020

5. Maternal-neonatal listeriosis

Author

Marc Lecuit, Caroline Charlier, Olivier Disson, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by the Institut Pasteur, Santé Publique France., DIAKITE, andrée, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)

Subjects
Microbiology (medical), placenta, [SDV]Life Sciences [q-bio], Immunology, macromolecular substances, Infectious and parasitic diseases, RC109-216, Biology, medicine.disease_cause, Microbiology, Infant, Newborn, Diseases, 03 medical and health sciences, Mice, Listeria monocytogenes, listeriosis, Risk Factors, newborn, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Placenta, medicine, Animals, Humans, Pregnancy Complications, Infectious, 030304 developmental biology, 0303 health sciences, Fetus, Pregnancy, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, 030306 microbiology, Infant, Newborn, medicine.disease, Infectious Disease Transmission, Vertical, infection, 3. Good health, Special Focus on Maternal-Fetal Infections, [SDV] Life Sciences [q-bio], fetus, Infectious Diseases, medicine.anatomical_structure, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Parasitology, Female, pregnancy, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Neonatal Listeriosis
Abstract

International audience; Listeriosis is a rare and severe foodborne infection caused by Listeria monocytogenes. It manifests as septicemia, neurolisteriosis, and maternal-fetal infection. In pregnancy, it may cause maternal fever, premature delivery, fetal loss, neonatal systemic and central nervous system infections. Maternal listeriosis is mostly reported during the 2nd and 3rd trimester of pregnancy, as sporadic cases or in the context of outbreaks. Strains belonging to clonal complexes 1, 4 and 6, referred to as hypervirulent, are the most associated to maternal-neonatal infections. Here we review the clinical, pathophysiological, and microbiological features of maternal-neonatal listeriosis.

Published
2020

6. Outbreak of Listeriosis in South Africa Associated with Processed Meat

Author

Vivien Essel, A.M. Shonhiwa, Kerrigan McCarthy, Tim Doyle, Nomsa P. Tau, Deon Mahoney, Alexandre Leclercq, Genevie Ntshoe, Olivier Disson, Mushal Allam, Robert W. Stewart, Adriano Duse, Mylène M. Maury, Teena Thomas, Hlengiwe M Ngomane, Linda Erasmus, Marc Lecuit, Arshad Ismail, Mathieu Tourdjman, Anthony M. Smith, Pierre Thouvenot, Juno Thomas, Bolele Disenyeng, Ntsieni Ramalwa, N. Govender, Lucille Blumberg, Nelesh P. Govender, Phuti Sekwadi, Shannon L. Smouse, Nicola Page, National Institute for Communicable Diseases [Johannesburg] (NICD), University of the Witwatersrand [Johannesburg] (WITS), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Université de Paris (UP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Université Paris Cité (UPCité)

Subjects
Adult, Male, Adolescent, [SDV]Life Sciences [q-bio], HIV Infections, 030204 cardiovascular system & hematology, Article, Disease Outbreaks, Foodborne Diseases, South Africa, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Environmental health, Humans, Medicine, Listeriosis, Processed meat, 030212 general & internal medicine, Pregnancy Complications, Infectious, Sex Distribution, Aged, Whole Genome Sequencing, business.industry, Infant, Newborn, Outbreak, General Medicine, Middle Aged, Listeria monocytogenes, Bacterial Typing Techniques, 3. Good health, Meat Products, Product Recalls and Withdrawals, Case-Control Studies, Food borne, HIV-1, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; BackgroundAn outbreak of listeriosis was identified in South Africa in 2017. The source was unknown.MethodsWe conducted epidemiologic, trace-back, and environmental investigations and used whole-genome sequencing to type Listeria monocytogenes isolates. A case was defined as laboratory-confirmed L. monocytogenes infection during the period from June 11, 2017, to April 7, 2018.ResultsA total of 937 cases were identified, of which 465 (50%) were associated with pregnancy; 406 of the pregnancy-associated cases (87%) occurred in neonates. Of the 937 cases, 229 (24%) occurred in patients 15 to 49 years of age (excluding those who were pregnant). Among the patients in whom human immunodeficiency virus (HIV) status was known, 38% of those with pregnancy-associated cases (77 of 204) and 46% of the remaining patients (97 of 211) were infected with HIV. Among 728 patients with a known outcome, 193 (27%) died. Clinical isolates from 609 patients were sequenced, and 567 (93%) were identified as sequence type 6 (ST6). In a case–control analysis, patients with ST6 infections were more likely to have eaten polony (a ready-to-eat processed meat) than those with non-ST6 infections (odds ratio, 8.55; 95% confidence interval, 1.66 to 43.35). Polony and environmental samples also yielded ST6 isolates, which, together with the isolates from the patients, belonged to the same core-genome multilocus sequence typing cluster with no more than 4 allelic differences; these findings showed that polony produced at a single facility was the outbreak source. A recall of ready-to-eat processed meat products from this facility was associated with a rapid decline in the incidence of L. monocytogenes ST6 infections.ConclusionsThis investigation showed that in a middle-income country with a high prevalence of HIV infection, L. monocytogenes caused disproportionate illness among pregnant girls and women and HIV-infected persons. Whole-genome sequencing facilitated the detection of the outbreak and guided the trace-back investigations that led to the identification of the source.

Published
2020

7. Author Correction: Hypervirulent Listeria monocytogenes clones’ adaptation to mammalian gut accounts for their association with dairy products

Author

Morgane Lavina, Mylène M. Maury, Pierre Thouvenot, Olivier Disson, Guillaume Vales, Alexandre Leclercq, Marc Lecuit, Sylvain Brisse, Hélène Bracq-Dieye, and Lei Huang

Subjects
Food Handling, Science, General Physics and Astronomy, Food Contamination, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Microbial ecology, Foodborne Diseases, 03 medical and health sciences, Listeria monocytogenes, Bacterial genetics, Drug Resistance, Bacterial, medicine, Animals, Humans, lcsh:Science, Author Correction, Ecosystem, 030304 developmental biology, Genetics, 0303 health sciences, Multidisciplinary, Virulence, 030306 microbiology, General Chemistry, Adaptation, Physiological, Clone Cells, Intestines, Meat Products, Biofilms, Anti-Infective Agents, Local, lcsh:Q, Dairy Products, Adaptation, Pathogens, Benzalkonium Compounds
Abstract

Listeria monocytogenes (Lm) is a major human and animal foodborne pathogen. Here we show that hypervirulent Lm clones, particularly CC1, are strongly associated with dairy products, whereas hypovirulent clones, CC9 and CC121, are associated with meat products. Clone adaptation to distinct ecological niches and/or different food products contamination routes may account for this uneven distribution. Indeed, hypervirulent clones colonize better the intestinal lumen and invade more intestinal tissues than hypovirulent ones, reflecting their adaption to host environment. Conversely, hypovirulent clones are adapted to food processing environments, with a higher prevalence of stress resistance and benzalkonium chloride tolerance genes and a higher survival and biofilm formation capacity in presence of sub-lethal benzalkonium chloride concentrations. Lm virulence heterogeneity therefore reflects the diversity of the ecological niches in which it evolves. These results also have important public health implications and may help in reducing food contamination and improving food consumption recommendations to at-risk populations.

Published
2019

8. IFITM proteins inhibit placental syncytiotrophoblast formation and promote fetal demise

Author

Thierry Fournier, Caroline Manet, Kenzo-Hugo Hillion, Thérèse Couderc, Emeline Perthame, Julian Buchrieser, Françoise Porrot, Séverine A. Degrelle, Marc Lecuit, Olivier Schwartz, Daniel A. Donahue, Quentin Nevers, Anne Dupressoir, Sylvie Souquere, Olivier Disson, Thierry Heidmann, Marlene V. Arroyo, Katinka Ruigrok, Xavier Montagutelli, Virus et Immunité - Virus and immunity, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et pharmacotoxicologie placentaire humaine : Microbiote pré & post natal (3PHM - UMR-S 1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Inovarion [Paris], Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique fonctionnelle de la Souris, Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Howard Hughes Medical Institute [New York] (HHMI), Howard Hughes Medical Institute (HHMI)-New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Rockefeller University [New York]-Columbia University Irving Medical Center (CUIMC), Analyse moléculaire, modélisation et imagerie de la maladie cancéreuse (AMMICa), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Virologie Structurale - Structural Virology, Rétrovirus endogènes et éléments rétroïdes des eucaryotes supérieurs (UMR 9196), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Vaccine Research Institute (VRI), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Work in the laboratory of O.S. is funded by Institut Pasteur, ANRS, Sidaction, the Vaccine Research Institute (ANR-10-LABX-77), Labex IBEID (ANR-10-LABX-62-IBEID), 'TIMTAMDEN' ANR-14-CE14-0029, 'CHIKV-Viro-Immuno' ANR-14-CE14-0015-01, CNRS and the Gilead HIV cure program. Work in the laboratory of M.L. is funded by Institut Pasteur, INSERM, ERC, Labex IBEID (ANR-10-LABX-62-IBEID), Institut Convergence, and Université Paris Descartes. C.M. was supported by a fellowship from grant no. ANR-10-LABX-62-IBEID. M.V.A. was supported by NSF GRFP grant no. 1644869., We thank members of the Virus and Immunity Unit for discussions and help, M. Maaran Rajah for critical reading of the manuscript. We thank patients who participated in the study. We also thank members of Embryology and Core Breeding teams (DTPS-C2RA-Central Animal Facility platform) for technical support with strain revivification, M. Cohen-Tannoudji for hosting mouse experiments. We thank the Cellular and Molecular Imaging facility of the Faculty of Pharmacy of Paris (UMS3612 CNRS/US25 INSERM), and the UtechS Photonic BioImaging (Imagopole)., ANR-10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-14-CE14-0029,TIMTAMDEN,Rôle des récepteurs TIM et TAM dans l'infection des cellules cibles par le virus de la dengue(2014), ANR-14-CE14-0015,CHIKV-Viro-Immuno,Multiplication et Relation avec l'hôte du virus Chikungunya(2014), Virus et Immunité - Virus and immunity (CNRS-UMR3569), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Vaccine Research Institute [Créteil, France] (VRI), Virus et Immunité, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Howard Hughes Medical Institute [New York], New York University School of Medicine, NYU System (NYU)-NYU System (NYU)-Columbia University Irving Medical Center (CUIMC)-Rockefeller University [New York], Virologie Structurale, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Institut des Maladies Génétiques Imagine [Paris], ANR-10-LABX-0077/10-LABX-0077,VRI,Initiative for the creation of a Vaccine Research Institute(2010), ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Centre National de la Recherche Scientifique (CNRS)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
0301 basic medicine, Fetal Resorption, [SDV]Life Sciences [q-bio], Endogeny, Pregnancy Proteins, Biology, Cell Fusion, Mice, 03 medical and health sciences, 0302 clinical medicine, Syncytiotrophoblast, Multinucleate, Pregnancy, Interferon, medicine, Animals, Humans, Fetal Death, Multidisciplinary, Cell fusion, Intracellular Signaling Peptides and Proteins, Gene Products, env, RNA-Binding Proteins, Trophoblast, Antigens, Differentiation, Transmembrane protein, Trophoblasts, 3. Good health, Cell biology, Poly I-C, 030104 developmental biology, medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Interferon Type I, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Apoptosis Regulatory Proteins, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract

Comment in Protecting fetal development. [Science. 2019]; International audience; Elevated levels of type I interferon (IFN) during pregnancy are associated with intrauterine growth retardation, preterm birth, and fetal demise through mechanisms that are not well understood. A critical step of placental development is the fusion of trophoblast cells into a multinucleated syncytiotrophoblast (ST) layer. Fusion is mediated by syncytins, proteins deriving from ancestral endogenous retroviral envelopes. Using cultures of human trophoblasts or mouse cells, we show that IFN-induced transmembrane proteins (IFITMs), a family of restriction factors blocking the entry step of many viruses, impair ST formation and inhibit syncytin-mediated fusion. Moreover, the IFN inducer polyinosinic:polycytidylic acid promotes fetal resorption and placental abnormalities in wild-type but not in Ifitm-deleted mice. Thus, excessive levels of IFITMs may mediate the pregnancy complications observed during congenital infections and other IFN-induced pathologies.

Published
2019

9. Atypical Hemolytic Listeria innocua Isolates Are Virulent, albeit Less than Listeria monocytogenes

Author

Alexandra Moura, Alexandre Leclercq, Morgane Lavina, Olivier Disson, Athmanya K. Eshwar, Marc Lecuit, Maria Fredriksson-Ahomaa, Pierre Thouvenot, Lei Huang, Roger Stephan, Centre National de Référence Listeria - Biologie des Infections (CNRL), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), Biologie des Infections - Biology of Infection, Université Paris Diderot, Sorbonne Paris Cité, Paris, France, Université Paris Diderot - Paris 7 (UPD7), University of Helsinki, Institute for Food Safety and Hygiene, University of Zürich [Zürich] (UZH), Service des Maladies infectieuses et tropicales [CHU Necker], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Institut des Maladies Génétiques Imagine [Paris], Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Universität Zürich [Zürich] = University of Zurich (UZH), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), University of Zurich, Freitag, Nancy E, and Lecuit, Marc

Subjects
inlA, L innocua, [SDV]Life Sciences [q-bio], 2405 Parasitology, LIPI, MESH: Virulence, medicine.disease_cause, MESH: Genome, Bacterial, MESH: Listeria monocytogenes, MESH: Bird Diseases, Feces, listeriosis, MESH: Listeria, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Ducks, MESH: Genomic Islands, MESH: Animals, Galliformes, MESH: Phylogeny, MESH: Bacterial Proteins, Phylogeny, 2. Zero hunger, 0303 health sciences, biology, Strain (chemistry), 2404 Microbiology, MESH: Feces, MESH: Galliformes, 3. Good health, Infectious Diseases, medicine.anatomical_structure, Ducks, MESH: Whole Genome Sequencing, Genomic Islands, Listeria, Immunology, Virulence, 610 Medicine & health, Spleen, Microbiology, 03 medical and health sciences, Listeria monocytogenes, Bacterial Proteins, medicine, Animals, Humans, Internalin, Serotyping, Gene, 10082 Institute of Food Safety and Hygiene, 030304 developmental biology, 2403 Immunology, MESH: Humans, Whole Genome Sequencing, 030306 microbiology, Bird Diseases, MESH: Serotyping, 2725 Infectious Diseases, biology.organism_classification, Pathogenicity island, Molecular Pathogenesis, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, virulence, L. innocua, MESH: Listeriosis, 570 Life sciences, Parasitology, Genome, Bacterial, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Listeria innocua is considered a nonpathogenic Listeria species. Natural atypical hemolytic L. innocua isolates have been reported but have not been characterized in detail. Here, we report the genomic and functional characterization of representative isolates from the two known natural hemolytic L. innocua clades. Whole-genome sequencing confirmed the presence of Listeria pathogenicity islands (LIPI) characteristic of Listeria monocytogenes species. Functional assays showed that LIPI-1 and inlA genes are transcribed, and the corresponding gene products are expressed and functional. Using in vitro and in vivo assays, we show that atypical hemolytic L. innocua is virulent, can actively cross the intestinal epithelium, and spreads systemi-cally to the liver and spleen, albeit to a lesser degree than the reference L. monocy-togenes EGDe strain. Although human exposure to hemolytic L. innocua is likely rare, these findings are important for food safety and public health. The presence of viru-lence traits in some L. innocua clades supports the existence of a common virulent ancestor of L. monocytogenes and L. innocua.

Published
2019

10. Listeria monocytogenes-associated endovascular infections: A study of 71 consecutive cases

Author

Guillaume Vales, Grégory Jouvion, Caroline Charlier, Gabrielle Coulpier, Olivier Disson, Marc Lecuit, Benoit Pilmis, Alexandre Leclercq, Pierre Thouvenot, Mylène M. Maury, Michka Shoai-Tehrani, Hélène Bracq-Dieye, Olivier Robineau, Laboratoire des Listeria, Centre National de Référence des Listeria, et Centre collaborateur de l’OMS pour la listériose d’origine alimentaire (CNR - CCOMS), Institut Pasteur [Paris], Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier de Tourcoing, Biologie des Infections - Biology of Infection, Neuropathologie expérimentale - Experimental neuropathology, Institut Pasteur [Paris]-Université Paris Descartes - Paris 5 (UPD5), Université Paris Descartes - Paris 5 (UPD5), This study received financial support from Institut Pasteur, Inserm and Santé Publique France., We thank Dr. Isabelle Serre (Gui Chauliac University Hospital, Montpellier, France), Dr. Valérie Hervieu (Edouard Herriot University Hospital, Lyon, France), Dr. Beatrice Luciani-Laillou (Périgueux, France) and Dr. Luc Marcellin (Hautepierre University Hospital, Strasbourg, France), David Hardy and Magali Tichit (Experimental Neuropathology Unit, Institut Pasteur, Paris) for their contribution to histopathology studies, as well as Giulia Nigro (Molecular Microbial Pathologenesis Unit, Institut Pasteur, Paris)., Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Université Paris Descartes - Paris 5 (UPD5), and DIAKITE, andrée

Subjects
0301 basic medicine, Male, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Prosthesis, medicine.disease_cause, Intracardiac injection, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Risk Factors, Medicine, Listeriosis, 030212 general & internal medicine, Hospital Mortality, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Endocarditis, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Heart Valve Prosthesis, Epidemiological Monitoring, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, France, Microbiology (medical), medicine.medical_specialty, 030106 microbiology, 03 medical and health sciences, Aneurysm, Listeria monocytogenes, Humans, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Aged, Retrospective Studies, business.industry, Retrospective cohort study, Endocarditis, Bacterial, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Surgery, Heart failure, Concomitant, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: Listeria monocytogenes-associated endovascular infections are not well characterized. Methods: Retrospective study of 71 culture-proven cases reported to the French National Reference Center for Listeria from 1993 to 2018. Results: Seventy-one cases were identified: 42 with vascular aneurysms/prosthetic infections, 27 with endocarditis, 2 with both. Fifty-eight were men (82%); median age was 75 years [46-92]; 93% reported co-morbidities (66/71), including 50% with immunosuppressive conditions. Vascular infections consisted of infected aneurysms (68%) or prosthetic graft infections (32%); vascular rupture was reported in 25/42 (60%). Tissue samples grew L. monocytogenes in 98% (43/44) and blood cultures in 64% (27/42). Endo-carditis cases involved prosthetic or native valves or intracardiac devices in respectively 62% (18/29), 28% (8/29) and 10% (3/29). Infected valves were aortic (62%, 16/26), mitral (31%, 8/26) or both (8%, 2/26); 38% patients required surgery; 45% displayed heart failure; 17% had concomitant neurolisteriosis. In-hospital mortality in vascular infections was 12% (5/42) and 41% (12/29) for Lm-associated endocarditis. Conclusions: Endovascular listeriosis is a rare but severe infection. It manifests as vascular infections and endocarditis, mostly in older patients with vascular or cardiac valve prosthetic devices and co-morbidities. Mortality in Lm-associated endocarditis is twice higher than with other pathogens, requiring prompt recognition and treatment.

Published
2019

11. Peyer’s patch myeloid cells infection by Listeria signals through gp38 + stromal cells and locks intestinal villus invasion

Author

James P. Di Santo, Grégory Jouvion, Sophie Dulauroy, Olivier Disson, Gérard Eberl, Nicolas Serafini, Grégoire Gessain, Marc Lecuit, Jean-Marie Jacob, Pierre Thouvenot, Lucie Peduto, Cindy Fevre, Camille Blériot, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Stroma, inflammation et réparation tissulaire - Stroma, Inflammation and Tissue Repair, Immunité Innée - Innate Immunity, Microenvironnement et Immunité - Microenvironment and Immunity, Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris] (IP), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was financed by Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Institut Carnot Pasteur Microbes et Santé, LabEx IBEID, the European Research Council grant Invadis, and the Agence Nationale de Recherche Organolist., We thank the members of the Biology of Infection Unit for their support. We thank Hélène Bierne for her implication in the initial phase of the project, Elena Tomasello and Eric Vivier for helpful discussions, Stéphane Dallongeville for image analysis, Sascha Cording, Morgane Lavina for technical help, and Hana Kammoun for critical reading. We thank Edith Gouin and Pascale Cossart for anti-Lm antibodies, Tracy Putoczki for Il11ra1−/− mice, Richard Flavell for Il22−/− mice, Bernhard Ryffel for IL23p19−/− mice, Laure Dumoutier, Jean-Christophe Renauld for anti–IL-22 antibody, and Gunnar C. Hansson for anti-MUC2C3 serum, ANR-15-CE15-0007,OrganoList,Interactions entre Listeria monocytogenes et la barrière intestinale(2015), ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 681829,ERC-CoG-2015,INVADIS(2016), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], DIAKITE, andrée, Interactions entre Listeria monocytogenes et la barrière intestinale - - OrganoList2015 - ANR-15-CE15-0007 - AAPG2015 - VALID, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, and Microbial invasion and dissemination within the host, mechanisms and effects - INVADIS - 2016-11-01 - 2021-10-31 - 681829 - VALID

Subjects
0301 basic medicine, [SDV]Life Sciences [q-bio], Interleukin 22, Mice, Peyer's Patches, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, Listeriosis, Myeloid Cells, Intestinal Mucosa, Research Articles, Mice, Knockout, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Membrane Glycoproteins, digestive, oral, and skin physiology, Colitis, Intestinal epithelium, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030220 oncology & carcinogenesis, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, STAT3 Transcription Factor, Stromal cell, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Biology, digestive system, Article, 03 medical and health sciences, medicine, Animals, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Immunity, Mucosal, Lamina propria, Innate immune system, Intestinal villus, Peyer's patch, Listeria monocytogenes, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Immunity, Innate, Epithelium, 030104 developmental biology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Stromal Cells, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Listeria monocytogenes (Lm) crosses the intestinal villus barrier via goblet cells (GCs). Disson et al. show that Lm infection of Peyer’s patch myeloid cells signals to villus stromal cells, leading to a decrease of GCs expressing luminally accessible E-cadherin, thereby blocking villus infection while favoring colitis., The foodborne pathogen Listeria monocytogenes (Lm) crosses the intestinal villus epithelium via goblet cells (GCs) upon the interaction of Lm surface protein InlA with its receptor E-cadherin. Here, we show that Lm infection accelerates intestinal villus epithelium renewal while decreasing the number of GCs expressing luminally accessible E-cadherin, thereby locking Lm portal of entry. This novel innate immune response to an enteropathogen is triggered by the infection of Peyer’s patch CX3CR1+ cells and the ensuing production of IL-23. It requires STAT3 phosphorylation in epithelial cells in response to IL-22 and IL-11 expressed by lamina propria gp38+ stromal cells. Lm-induced IFN-γ signaling and STAT1 phosphorylation in epithelial cells is also critical for Lm-associated intestinal epithelium response. GC depletion also leads to a decrease in colon mucus barrier thickness, thereby increasing host susceptibility to colitis. This study unveils a novel innate immune response to an enteropathogen, which implicates gp38+ stromal cells and locks intestinal villus invasion, but favors colitis., Graphical Abstract

Published
2018

12. Le rôle critique de la PI3-kinase dans la traversée des barrières de l’hôte parListeria monocytogenes

Author

Grégoire Gessain, Olivier Disson, and Marc Lecuit

Subjects
0301 basic medicine, Permissiveness, Chemistry, Kinase, General Medicine, Phosphatidylinositol 3-Kinases, medicine.disease_cause, Blood–brain barrier, General Biochemistry, Genetics and Molecular Biology, Microbiology, 03 medical and health sciences, Enzyme activator, 030104 developmental biology, medicine.anatomical_structure, Listeria monocytogenes, Intestinal mucosa, Placenta, medicine
Published
2016

13. Translocation and dissemination to target neurons of botulinum neurotoxin type B in the mouse intestinal wall

Author

Olivier Disson, Carolina Varela-Chavez, Jordi Molgó, Alain Vandewalle, Georges Michel Haustant, Chloé Connan, Christelle Mazuet, Marc Lecuit, and Michel R. Popoff

Subjects
0301 basic medicine, Cell type, Immunology, Chromosomal translocation, Anatomy, Biology, Endocytosis, Microbiology, Intestinal epithelium, Synaptotagmin 1, Cell biology, 03 medical and health sciences, 030104 developmental biology, medicine.anatomical_structure, Cell surface receptor, Virology, Lymph circulation, medicine, Neuron
Abstract

Botulinum neurotoxins (BoNTs) are responsible for severe flaccid paralysis (botulism), which in most cases enter the organism via the digestive tract and then disseminate into the blood or lymph circulation to target autonomic and motor nerve endings. The passage way of BoNTs alone or in complex forms with associated nontoxic proteins through the epithelial barrier of the digestive tract still remains unclear. Here, we show using an in vivo model of mouse ligated intestinal loop that BoNT/B alone or the BoNT/B C-terminal domain of the heavy chain (HCcB), which interacts with cell surface receptors, translocates across the intestinal barrier. The BoNT/B or HCcB translocation through the intestinal barrier occurred via an endocytosis-dependent mechanism within 10-20 min, because Dynasore, a potent endocytosis inhibitor, significantly prevented BoNT/B as well as HCcB translocation. We also show that HCcB or BoNT/B specifically targets neuronal cells and neuronal extensions in the intestinal submucosa and musculosa expressing synaptotagmin, preferentially cholinergic neurons and to a lower extent other neuronal cell types, notably serotonergic neurons. Interestingly, rare intestinal epithelial cells accumulated HCcB suggesting that distinct cell types of the intestinal epithelium, still undefined, might mediate efficient translocation of BoNT/B.

Published
2015

14. Spontaneous Loss of Virulence in Natural Populations of Listeria monocytogenes

Author

Mariela Scortti, Alexandra Moura, Lei Han, Guillaume Vales, Alexandre Leclercq, Olivier Disson, Marc Lecuit, Hélène Bracq-Dieye, Mylène M. Maury, Edith Gouin, José A. Vázquez-Boland, Viviane Chenal-Francisque, Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Edinburgh, Biologie des Infections - Biology of Infection, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Work in M.L.'s laboratory was supported by Institut Pasteur, Inserm, LabEx IBEID, the European Research Council, and Santé Publique France. Work in J.A.V.-B.'s laboratory was supported by the Wellcome Trust (program grant WT074020MA) and partially by core Roslin Institute funding from BBSRC (BB/J004227/1), We acknowledge Anne Morvan, Thomas Cantinelli, Nathalie Tessaud-Rita and Laetitia Bellon for their help in strain collection and isolation at the National Reference Centre for Listeria. We thank Pascale Cossart for providing antibodies against LLO and the Institut Pasteur P2M platform for genome sequencing., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), DIAKITE, andrée, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), Centre National de Référence Listeria - Biologie des Infections (CNRL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Institut des Maladies Génétiques Imagine [Paris], and ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010)

Subjects
0301 basic medicine, Erythrocytes, MESH: Selection, Genetic, Mutant, MESH: Heat-Shock Proteins, MESH: Virulence, medicine.disease_cause, MESH: Listeria monocytogenes, Severity of Illness Index, MESH: Recombinant Proteins, Hemolysin Proteins, Mice, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Listeriosis, MESH: Animals, Cloning, Molecular, MESH: Phylogeny, Pathogen, MESH: Bacterial Proteins, Heat-Shock Proteins, Phylogeny, Mice, Inbred BALB C, MESH: Gene Expression Regulation, Bacterial, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, MESH: Erythrocytes, Listeriolysin O, Biological Evolution, spontaneous mutations, MESH: Amino Acid Substitution, MESH: Hemolysis, Recombinant Proteins, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Hemolysin Proteins, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Peptide Termination Factors, Peptide Termination Factors, Transposable element, MESH: Mutation, Bacterial Toxins, 030106 microbiology, Immunology, MESH: Mice, Inbred BALB C, Virulence, Molecular Genomics, MESH: Biological Evolution, Biology, Microbiology, Frameshift mutation, 03 medical and health sciences, Bacterial Proteins, Listeria monocytogenes, MESH: Severity of Illness Index, medicine, genomics, Animals, Humans, MESH: Cloning, Molecular, Selection, Genetic, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Gene, MESH: Mice, MESH: Humans, Gene Expression Regulation, Bacterial, biochemical phenomena, metabolism, and nutrition, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, virulence, Amino Acid Substitution, MESH: Bacterial Toxins, MESH: Listeriosis, Mutation, Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, hemolysis, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

The pathogenesis of Listeria monocytogenes depends on the ability of this bacterium to escape from the phagosome of the host cells via the action of the pore-forming toxin listeriolysin O (LLO). Expression of the LLO-encoding gene ( hly ) requires the transcriptional activator PrfA, and both hly and prfA genes are essential for L. monocytogenes virulence. Here, we used the hemolytic activity of LLO as a phenotypic marker to screen for spontaneous virulence-attenuating mutations in L. monocytogenes . Sixty nonhemolytic isolates were identified among a collection of 57,820 confirmed L. monocytogenes strains isolated from a variety of sources (0.1%). In most cases (56/60; 93.3%), the nonhemolytic phenotype resulted from nonsense, missense, or frameshift mutations in prfA . Five strains carried hly mutations leading to a single amino acid substitution (G299V) or a premature stop codon causing strong virulence attenuation in mice. In one strain, both hly and gshF (encoding a glutathione synthase required for full PrfA activity) were missing due to genomic rearrangements likely caused by a transposable element. The PrfA/LLO loss-of-function (PrfA − /LLO − ) mutants belonged to phylogenetically diverse clades of L. monocytogenes , and most were identified among nonclinical strains (57/60). Consistent with the rare occurrence of loss-of-virulence mutations, we show that prfA and hly are under purifying selection. Although occurring at a low frequency, PrfA − /LLO − mutational events in L. monocytogenes lead to niche restriction and open an evolutionary path for obligate saprophytism in this facultative intracellular pathogen.

Published
2017

15. Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity

Author

Mylène M. Maury, Olivier Disson, Marc Lecuit, Sophie Roussel, Yu Huan Tsai, Alexis Criscuolo, Sylvain Brisse, Viviane Chenal-Francisque, Alexandre Leclercq, Eduardo P. C. Rocha, Caroline Charlier, Marie Touchon, Anne Brisabois, Charlotte Gaultier, DIAKITE, andrée, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Subversive pro- and anti-inflammation trade-offs promote infection by Listeria monocytogenes - Infect-ERA/0001/2013 - - FCT::2014-09-01 - 2017-08-31 - 137216 - VALID, Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Génomique évolutive des Microbes / Microbial Evolutionary Genomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université Paris Descartes - Paris 5 (UPD5), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Université Paris-Est (UPE), Laboratoire de sécurité des aliments de Maisons-Alfort (LSAl), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This study was funded by the Institut Pasteur, INSERM, from the French government's Investissement d'Avenir program, Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases' (grant ANR-10-LABX-62-IBEID), the European Research Council (ERC), ERANET Proantilis, the Programme Hospitalier de Recherche Clinique MONALISA and the Programme de Recherche Translationnelle (PTR) ANSES–Institut Pasteur. Listeriosis surveillance in France is funded by the Institut de Veille Sanitaire (InVS) and the Institut Pasteur., We thank C. Soto Alvarez, G. Pontdeme, T. Cantinelli and L. Diancourt for their contributions to MLST data production and analysis, and S. Roche for providing low-virulence strains for genome sequencing. We also thank D. Mornico (Center of Bioinformatics, Biostatistics and Integrative Biology of the Institut Pasteur) for his help with the submission of genome reads and assemblies., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 137216,FCT::,Infect-ERA/2013,Infect-ERA/0001/2013(2014), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)

Subjects
Central Nervous System, 0301 basic medicine, 030106 microbiology, Virulence, Genomics, Biology, medicine.disease_cause, Article, Microbiology, Mice, 03 medical and health sciences, Listeria monocytogenes, Phylogenetics, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Gene cluster, Genetics, medicine, Animals, Humans, Listeriosis, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Phylogeny, 2. Zero hunger, Comparative genomics, Biodiversity, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 030104 developmental biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Humanized mouse, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Microbial genetics, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Genome-Wide Association Study
Abstract

Corrigendum: Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity. [Nat Genet. 2017]Erratum: Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity. [Nat Genet. 2017]Comment in Biodiversity and hypervirulence of Listeria monocytogenes. [Nat Genet. 2016] Bacterial GWAS: not just gilding the lily. [Nat Rev Microbiol. 2016]; International audience; Microbial pathogenesis studies are typically performed with reference strains, thereby overlooking within-species heterogeneity in microbial virulence. Here we integrated human epidemiological and clinical data with bacterial population genomics to harness the biodiversity of the model foodborne pathogen Listeria monocytogenes and decipher the basis of its neural and placental tropisms. Taking advantage of the clonal structure of this bacterial species, we identify clones epidemiologically associated either with food or with human central nervous system (CNS) or maternal-neonatal (MN) listeriosis. The latter clones are also most prevalent in patients without immunosuppressive comorbidities. Strikingly, CNS- and MN-associated clones are hypervirulent in a humanized mouse model of listeriosis. By integrating epidemiological data and comparative genomics, we have uncovered multiple new putative virulence factors and demonstrate experimentally the contribution of the first gene cluster mediating L. monocytogenes neural and placental tropisms. This study illustrates the exceptional power in harnessing microbial biodiversity to identify clinically relevant microbial virulence attributes

Published
2016

16. PI3-kinase activation is critical for host barrier permissiveness to Listeria monocytogenes

Author

Olivier Disson, Caroline Charlier, Solène Grayo, Yu Huan Tsai, Marc Lecuit, Pascale Cossart, Grégoire Gessain, Laetitia Travier, Matteo Bonazzi, Cellule Pasteur, Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur, Inserm, FRM, Ville de Paris, fondation AXA, fondation BNP Paribas, LabEx IBEID, ERC, European Project: 261157,EC:FP7:ERC,ERC-2010-StG_20091118,MICROTRANS(2010), Disson, Olivier, Microbial translocation across host barriers - MICROTRANS - - EC:FP7:ERC2010-11-01 - 2016-10-31 - 261157 - VALID, Lecuit, Marc, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), and Centre National de Référence Listeria - Biologie des Infections (CNRL)

Subjects
Permissiveness, Immunology, Plasma protein binding, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine.disease_cause, Article, Enzyme activator, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, Listeria monocytogenes, Intestinal mucosa, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Immunology and Allergy, Animals, Humans, Listeriosis, Subcellular Processes, 030304 developmental biology, 0303 health sciences, Phosphoinositide 3-kinase, biology, Cadherin, SDV:MP:BAC, Cell Biology, bacterial infections and mycoses, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Cell biology, SDV:BC:IC, 030220 oncology & carcinogenesis, Host-Pathogen Interactions, biology.protein, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Female, Organisation et fonctions cellulaires, Signal transduction, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, SDV:MHEP:MI
Abstract

Gessain et al. explore how Listeria monocytogenes facilitates disseminated infection through host epithelial barriers using two of its surface proteins, InlA and InlB. By combining in vitro and in vivo approaches using intestinal and placental mouse and human tissues, they find a differential requirement for InlA and InlB in tissue invasiveness, with a critical role for PI3K activation., Invasion of nonphagocytic cells, a critical property of Listeria monocytogenes (Lm) that enables it to cross host barriers, is mediated by the interaction of two bacterial surface proteins, InlA and InlB, with their respective receptors E-cadherin and c-Met. Although InlA–E-cadherin interaction is necessary and sufficient for Lm crossing of the intestinal barrier, both InlA and InlB are required for Lm crossing of the placental barrier. The mechanisms underlying these differences are unknown. Phosphoinositide 3-kinase (PI3-K) is involved in both InlA- and InlB-dependent pathways. Indeed, InlA-dependent entry requires PI3-K activity but does not activate it, whereas InlB–c-Met interaction activates PI3-K. We show that Lm intestinal target cells exhibit a constitutive PI3-K activity, rendering InlB dispensable for InlA-dependent Lm intestinal barrier crossing. In contrast, the placental barrier does not exhibit constitutive PI3-K activity, making InlB necessary for InlA-dependent Lm placental invasion. Here, we provide the molecular explanation for the respective contributions of InlA and InlB to Lm host barrier invasion, and reveal the critical role of InlB in rendering cells permissive to InlA-mediated invasion. This study shows that PI3-K activity is critical to host barrier permissiveness to microbes, and that pathogens exploit both similarities and differences of host barriers to disseminate.

Published
2015

17. Liver-Resident Macrophage Necroptosis Orchestrates Type 1 Microbicidal Inflammation and Type-2-Mediated Tissue Repair during Bacterial Infection

Author

Grégory Jouvion, Camille Blériot, Olivier Disson, Théo Dupuis, Marc Lecuit, Gérard Eberl, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Histopathologie humaine et Modèles animaux, Institut Pasteur [Paris], Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), This work was financed by Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Institut Carnot, Fondation pour la Recherche Médicale, Ville de Paris, Fondation BNP Paribas, LabEx IBEID, the European Research Council, and Listress EU program., We thank the members of the Biology of Infection Unit, and in particular Y.H. Tsai. We thank G. Milon and S. Berrè for helpful discussions and critical reading of the manuscript. We thank H. Bierne for her contribution in the initial phase of the project and P. Cossart for providing the Lm Δhly mutant. We thank T. Walzer at ENS Lyon for Ccr2−/− mice, Ph. Bousso and F. Montalvao for MaFIA-GFP mice and helpful discussions, M. Leite de Moraes for Il4−/− mice, B. Ryffel for Il1rl1−/− mice, V. Dixit for Rip3−/− mice, T. Taniguchi for Irf3−/− mice, R. Menard for Flk1-gfp mice, and M. Albert and N. Yatim for Casp1−/− and Ifnar−/− mice and helpful discussions. We thank S. Novault of the PFC at Institut Pasteur and N. Sérafini for their help in the FACS experiments., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 116472,FCT::,ERA-PTG/2010,ERA-PTG/0003/2010(2011), Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Institut des Maladies Génétiques Imagine [Paris], ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
MESH: Inflammation, Necrosis, Cellular differentiation, [SDV]Life Sciences [q-bio], Complement Pathway, Alternative, MESH: Listeria monocytogenes, MESH: Monocytes, Monocytes, Mice, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Macrophage, Immunology and Allergy, Homeostasis, Listeriosis, MESH: Animals, MESH: Phagocytosis, Cells, Cultured, 0303 health sciences, Kupffer cell, Cell Differentiation, medicine.anatomical_structure, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Liver, MESH: Homeostasis, [SDV.IMM]Life Sciences [q-bio]/Immunology, medicine.symptom, MESH: Cells, Cultured, MESH: Cell Differentiation, MESH: Interleukins, MESH: Interleukin-33, Kupffer Cells, Necroptosis, Immunology, Inflammation, Mice, Inbred Strains, Biology, MESH: Mice, Inbred Strains, 03 medical and health sciences, Immune system, Phagocytosis, medicine, Animals, MESH: Mice, 030304 developmental biology, MESH: Necrosis, Wound Healing, Monocyte, Interleukins, MESH: Interleukin-4, Interleukin-33, Listeria monocytogenes, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Wound Healing, MESH: Kupffer Cells, MESH: Listeriosis, Interleukin-4, MESH: Complement Pathway, Alternative, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030215 immunology, MESH: Liver
Abstract

International audience; Kupffer cells, the phagocytes of fetal origin that line the liver sinusoids, are key contributors of host defense against enteroinvasive bacteria. Here, we found that infection by Listeria monocytogenes induced the early necroptotic death of Kupffer cells, which was followed by monocyte recruitment and an anti-bacterial type 1 inflammatory response. Kupffer cell death also triggered a type 2 response that involved the hepatocyte-derived alarmin interleukin-33 (IL-33) and basophil-derived interleukin-4 (IL-4). This led to the alternative activation of the monocyte-derived macrophages recruited to the liver, which thereby replaced ablated Kupffer cells and restored liver homeostasis. Kupffer cell death is therefore a key signal orchestrating type 1 microbicidal inflammation and type-2-mediated liver repair upon infection. This indicates that beyond the classical dichotomy of type 1 and type 2 responses, these responses can develop sequentially in the context of a bacterial infection and act interdependently, orchestrating liver immune responses and return to homeostasis, respectively.

Published
2015

18. Erratum: Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity

Author

Caroline Charlier, Alexis Criscuolo, Yu-Huan Tsai, Olivier Disson, Marie Touchon, Viviane Chenal-Francisque, Sophie Roussel, Eduardo P. C. Rocha, Alexandre Leclercq, Charlotte Gaultier, Mylène M. Maury, Sylvain Brisse, Anne Brisabois, and Marc Lecuit

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, Listeria monocytogenes, Genetics, medicine, Biodiversity, Biology, medicine.disease_cause, Microbiology
Abstract

Nat. Genet. 48, 308–313 (2016); published online 1 February 2016; corrected after print 6 March 2017 In the version of this article initially published, the titles of the x axes in Figure 5b and 5c should have been “Brain/blood CFU ratio” instead of “Blood/brain CFU ratio,” and the title of the z axis in Figure 2c should have been “% of isolates” instead of “Number of isolates.

Published
2017

19. Erratum: Corrigendum: Uncovering Listeria monocytogenes hypervirulence by harnessing its biodiversity

Author

Anne Brisabois, Eduardo P. C. Rocha, Marie Touchon, Sophie Roussel, Viviane Chenal-Francisque, Yu-Huan Tsai, Caroline Charlier, Marc Lecuit, Alexandre Leclercq, Mylène M. Maury, Charlotte Gaultier, Olivier Disson, Sylvain Brisse, and Alexis Criscuolo

Subjects
0301 basic medicine, 03 medical and health sciences, 030104 developmental biology, Listeria monocytogenes, Cns infections, Genetics, Biodiversity, medicine, Biology, medicine.disease_cause, Microbiology
Abstract

Nat. Genet. 48, 308–313 (2016); published online 1 February 2016; corrected after print 6 March 2017 In the version of this article initially published, in Figure 2b, in the panel called “CNS infections” the bar of CC3 should have been represented in red and the one of CC121 should have been represented in blue.

Published
2017

20. Méningite néonatale à streptocoque du groupe B

Author

Isabelle Tardieux, Claire Poyart, Marc Lecuit, Abdelouhab Bouaboud, Olivier Disson, Patrick Trieu-Cuot, Asmaa Tazi, and Samuel Bellais

Subjects
0303 health sciences, 03 medical and health sciences, 030306 microbiology, General Medicine, General Biochemistry, Genetics and Molecular Biology, 030304 developmental biology, 3. Good health
Abstract

Le streptocoque du groupe B (SGB, Streptococcus agalactiae ) est une bacterie capsulee a Gram positif commensale des voies digestives et vaginales retrouvee chez 20 a 30 % des adultes sains. Son interet en medecine humaine reside principalement dans le fait que cette bacterie est la premiere cause d’infections neonatales invasives (septicemies, meningites) et un pathogene d’importance croissante chez l’adulte, en particulier chez le sujet âge et les individus porteurs de pathologies sousjacentes [].

Published
2011

21. Concepts and Mechanisms: Crossing Host Barriers

Author

Kelly S. Doran, Olivier Disson, Anirban Banerjee, Marc Lecuit, San Diego State University (SDSU), University of California [San Diego] (UC San Diego), University of California, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Work on the BBB and bacterial meningitis in K.S.D.’s laboratory is supported by funding from the National Institutes of Health/National Institute of Neurological Disorders and Stroke (grant No. RO1NS051247). Work in M.L’s laboratory is supported by Institut Pasteur, INSERM, ERC, FRM, Ville de Paris, Labex IBEID, Listress, and ICRES EU Programs and Fondation BNP-Paribas. The authors declare no competing financial interests., The authors thank their respective laboratory members for their help and support and apologize to researchers whose work has not been discussed in detail or reviewed here because of space constraints., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-10-PATH-0001,LISTRESS(2010), University of California (UC), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
Immune defense, Placenta, [SDV]Life Sciences [q-bio], Biology, Bacterial translocation, Bacterial Adhesion, General Biochemistry, Genetics and Molecular Biology, Microbiology, 03 medical and health sciences, Phagocytosis, Intestinal mucosa, Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animals, Humans, Barrier integrity, Parasites, Intestinal Mucosa, Skin, 030304 developmental biology, Inflammation, 0303 health sciences, Bacteria, 030306 microbiology, Host (biology), Cell biology, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Blood-Brain Barrier, Bacterial Translocation, Host-Pathogen Interactions, Viruses, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Perspectives
Abstract

International audience; The human body is bordered by the skin and mucosa, which are the cellular barriers that define the frontier between the internal milieu and the external nonsterile environment. Additional cellular barriers, such as the placental and the blood-brain barriers, define protected niches within the host. In addition to their physiological roles, these host barriers provide both physical and immune defense against microbial infection. Yet, many pathogens have evolved elaborated mechanisms to target this line of defense, resulting in a microbial invasion of cells constitutive of host barriers, disruption of barrier integrity, and systemic dissemination and invasion of deeper tissues. Here we review representative examples of microbial interactions with human barriers, including the intestinal, placental, and blood-brain barriers, and discuss how these microbes adhere to, invade, breach, or compromise these barriers.

Published
2013

22. Murinization of internalin extends its receptor repertoire, altering Listeria monocytogenes cell tropism and host responses

Author

Yu Huan Tsai, Olivier Disson, Hélène Bierne, Marc Lecuit, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7), Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université Paris Descartes - Paris 5 (UPD5), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur, Institut National de la Sante et de la Recherche Medicale, Fondation pour la Recherche Medicale, Ville de Paris, Fondation BNP Paribas, Listress EU program, LabEx IBEID, European Research Council, Institut Pasteur (Pasteur-Paris University International PhD Program), Institut Carnot, INRA, French National Research Agency (ANR blanc), Ligue Contre le Cancer, ProdInra, Migration, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)

Subjects
[SDV]Life Sciences [q-bio], medicine.disease_cause, Mice, Intestinal mucosa, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Listeriosis, Intestinal Mucosa, Biology (General), Internalization, media_common, 0303 health sciences, Cadherins, Intestinal epithelium, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Female, [SDV.MP.PAR] Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Research Article, QH301-705.5, media_common.quotation_subject, Immunology, Mice, Transgenic, Biology, Microbiology, 03 medical and health sciences, Model Organisms, Bacterial Proteins, Listeria monocytogenes, Virology, Genetics, medicine, Animals, Humans, Internalin, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Molecular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Tropism, 030304 developmental biology, Innate immune system, 030306 microbiology, RC581-607, bacterial infections and mycoses, Disease Models, Animal, Humanized mouse, Parasitology, Immunologic diseases. Allergy
Abstract

Listeria monocytogenes (Lm) is an invasive foodborne pathogen that leads to severe central nervous system and maternal-fetal infections. Lm ability to actively cross the intestinal barrier is one of its key pathogenic properties. Lm crosses the intestinal epithelium upon the interaction of its surface protein internalin (InlA) with its host receptor E-cadherin (Ecad). InlA-Ecad interaction is species-specific, does not occur in wild-type mice, but does in transgenic mice expressing human Ecad and knock-in mice expressing humanized mouse Ecad. To study listeriosis in wild-type mice, InlA has been “murinized” to interact with mouse Ecad. Here, we demonstrate that, unexpectedly, murinized InlA (InlAm) mediates not only Ecad-dependent internalization, but also N-cadherin-dependent internalization. Consequently, InlAm-expressing Lm targets not only goblet cells expressing luminally-accessible Ecad, as does Lm in humanized mice, but also targets villous M cells, which express luminally-accessible N-cadherin. This aberrant Lm portal of entry results in enhanced innate immune responses and intestinal barrier damage, both of which are not observed in wild-type Lm-infected humanized mice. Murinization of InlA therefore not only extends the host range of Lm, but also broadens its receptor repertoire, providing Lm with artifactual pathogenic properties. These results challenge the relevance of using InlAm-expressing Lm to study human listeriosis and in vivo host responses to this human pathogen., Author Summary Co-evolution of microbes with their hosts can select stringently specific host-microbe interactions at the cell, tissue and species levels. Listeria monocytogenes (Lm) is a foodborne pathogen that causes a deadly systemic infection in humans. Lm crosses the intestinal epithelium upon the interaction of its surface protein InlA with E-cadherin (Ecad). InlA-Ecad interaction is species-specific, does not occur in wild-type mice, but does in transgenic mice expressing human Ecad and knock-in mice expressing humanized mouse Ecad. To study listeriosis in wild-type mice, InlA has been “murinized” to interact with mouse Ecad. Here, we demonstrate that in addition to interacting with mouse Ecad, InlAm also uses N-cadherin as a receptor, whereas InlA does not. This artifactual InlAm-N-cadherin interaction promotes bacterial translocation across villous M cells, a cell type which is not targeted by InlA-expressing bacteria. This leads to intestinal inflammation and intestinal barrier damage, both of which are not seen in humans and humanized mouse models permissive to InlA-Ecad interaction. These results challenge the relevance of using InlAm-expressing Lm as a model to study human listeriosis and host responses to this pathogen. They also illustrate that caution must be exercised before using “murinized” pathogens to study human infectious diseases.

Published
2013

23. ActA promotes Listeria monocytogenes aggregation, intestinal colonization and carriage

Author

Jean-Marc Ghigo, Marc Lecuit, Viviane Chenal-Francisque, Edith Gouin, Olivier Disson, Alexandre Dufour, Stéphanie Guadagnini, Pascale Cossart, Laetitia Travier, Jean-Christophe Olivo-Marin, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Microscopie ultrastructurale (plate-forme), Institut Pasteur [Paris], Interactions Bactéries-Cellules (UIBC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Analyse d'Images Quantitative (AIQ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), Génétique des Biofilms, Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], This work received financial support of the Institut Pasteur (http://www.pasteur.fr/ip/easysite/pasteur/en), the Institut National de la Santé et de la Recherche Médicale (Inserm) (http://www.inserm.fr/), the Fondation pour la Recherche Médicale (FRM) (http://www.frm.org/), the European Research Council (ERC) (http://erc.europa.eu/), the Mairie de Paris (http://www.paris.fr/) and the BNP Paribas Foundation (http://www.bnpparibas.com/nous-connaitre/mecenat/fondation-bnp-paribas)., We thank Cindy Fèvre, Delphine Judith, Camille Blériot and Lilliana Radoshevich, Alexandre Leclercq and Marie-Christine Prevost for helpful discussions and critical reading of the manuscript. We thank Didier Cabanes, the students of the 2003–2004 Institut Pasteur Microbiology Course and Prof. O Dussurget for the EGDe ΔactA (BUG2167) and EGD ΔprfA (BUG2141) strains., Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Bacterial Diseases, [SDV]Life Sciences [q-bio], Pathogenesis, medicine.disease_cause, Feces, Mice, fluids and secretions, Intestinal mucosa, Gastrointestinal tract, Listeriosis, Gastrointestinal Infections, Intestinal Mucosa, Biology (General), Pathogen, Cecum, 0303 health sciences, Microbial Growth and Development, Animal Models, Bacterial Pathogens, Host-Pathogen Interaction, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Host-Pathogen Interactions, embryonic structures, Medicine, Bacterial and Foodborne Illness, Intracellular, Research Article, Virulence Factors, Colon, QH301-705.5, Immunology, Virulence, Motility, Gastroenterology and Hepatology, macromolecular substances, Biology, Microbiology, Cell Line, 03 medical and health sciences, Model Organisms, Listeria monocytogenes, Bacterial Proteins, Virology, Genetics, medicine, Animals, Humans, Actin polymerization, Molecular Biology, Microbial Pathogens, 030304 developmental biology, FLOW BIOFILM FORMATION, ARP2/3 COMPLEX, SURFACE PROTEIN, VIRULENCE GENES, EGD-E, DISINFECTANT RESISTANCE, FECAL CARRIAGE, TAIL FORMATION, E-CADHERIN, MOTILITY, Intracellular pathogens, 030306 microbiology, Intracellular parasite, Biofilm, technology, industry, and agriculture, Membrane Proteins, Bacteriology, RC581-607, Actins, Disease Models, Animal, Bacterial biofilms, Biofilms, bacteria, Parasitology, Immunologic diseases. Allergy
Abstract

Listeria monocytogenes (Lm) is a ubiquitous bacterium able to survive and thrive within the environment and readily colonizes a wide range of substrates, often as a biofilm. It is also a facultative intracellular pathogen, which actively invades diverse hosts and induces listeriosis. So far, these two complementary facets of Lm biology have been studied independently. Here we demonstrate that the major Lm virulence determinant ActA, a PrfA-regulated gene product enabling actin polymerization and thereby promoting its intracellular motility and cell-to-cell spread, is critical for bacterial aggregation and biofilm formation. We show that ActA mediates Lm aggregation via direct ActA-ActA interactions and that the ActA C-terminal region, which is not involved in actin polymerization, is essential for aggregation in vitro. In mice permissive to orally-acquired listeriosis, ActA-mediated Lm aggregation is not observed in infected tissues but occurs in the gut lumen. Strikingly, ActA-dependent aggregating bacteria exhibit an increased ability to persist within the cecum and colon lumen of mice, and are shed in the feces three order of magnitude more efficiently and for twice as long than bacteria unable to aggregate. In conclusion, this study identifies a novel function for ActA and illustrates that in addition to contributing to its dissemination within the host, ActA plays a key role in Lm persistence within the host and in transmission from the host back to the environment., Author Summary Listeria monocytogenes (Lm) is a ubiquitous bacterium that survives and thrives within the environment, and a facultative intracellular pathogen that induces listeriosis. So far, these two complementary facets of Lm biology have been studied independently. Here we identify ActA, which is a major Lm virulence determinant mediating actin-based motility, as critical for bacterial aggregation and biofilm formation. ActA promotes Lm aggregation via direct ActA-ActA interaction and ActA C-terminal region, which is not involved in actin polymerization, is essential for aggregation. Whereas ActA-mediated Lm aggregation is not observed in infected tissues, it occurs in the gut lumen. Strikingly, ActA-dependent aggregating bacteria exhibit an increased ability to persist within the gut lumen, and are shed in the feces three order of magnitude more and for twice as long than bacteria unable to aggregate. This study identifies a novel function for ActA, which plays a key role in Lm persistence within the host and transmission.

Published
2013

24. Targeting of the central nervous system by Listeria monocytogenes

Author

Marc Lecuit, Olivier Disson, DIAKITE, andrée, Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence des Listeria-G5 Microorganismes et Barrières de l'Hôte (CNR-CCOMS), Institut Pasteur [Paris] (IP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris], CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris]

Subjects
[SDV]Life Sciences [q-bio], Meningitis, Listeria, Review, medicine.disease_cause, MESH: Listeria monocytogenes, MESH: Blood-Brain Barrier, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Meningoencephalitis, Ruminants, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Blood-Brain Barrier, MESH: Ruminants, Host-Pathogen Interactions, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Meningitis, Microbiology (medical), Immunology, Central nervous system, Biology, Blood–brain barrier, Microbiology, 03 medical and health sciences, Listeria monocytogenes, In vivo, medicine, Animals, Humans, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, MESH: Humans, 030306 microbiology, Intracellular parasite, MESH: Host-Pathogen Interactions, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, In vitro, Disease Models, Animal, Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Disease Models, Animal, MESH: Meningitis, Listeria, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Among bacteria that reach the central nervous system (CNS), Listeria monocytogenes (Lm) is one of deadliest, in human and ruminant. This facultative intracellular bacterium has the particularity to induce meningitis, meningoencephalitis and rhombencephalitis. Mechanisms by which Lm accesses the CNS remain poorly understood, but two major routes of infection have been proposed, based on clinical, in vitro and in vivo observations. A retrograde neural route is likely to occur in ruminants upon crossing of the oral epithelium, and this probably accounts for the observation that Lm induces almost exclusively rhombencephalitis in these animals. In contrast, the hematogenous route is likely the most frequent in human, in whom bacteria circulating in the blood, either free or associated with leukocytes are thought to breach the blood-brain barrier. New animal models that faithfully reproduce the hallmarks of human neurolisterisosis will allow addressing the molecular mechanisms underlying Lm ability to induce CNS disease, and improve our understanding of the pathophysiology of this deadly infection.

Published
2012

25. Transcytosis of Listeria monocytogenes across the intestinal barrier upon specific targeting of goblet cell accessible E-cadherin

Author

Pascale Cossart, Théodora Niault, Marc Lecuit, Olivier Disson, Georgios Nikitas, Chantal Deschamps, Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Centre National de Référence des Listeria-G5 Microorganismes et Barrières de l'Hôte (CNR-CCOMS), Institut Pasteur [Paris], Georgios Nikitas received a Marie Curie Early Stage Research Training fellowship from the Intrapath program, EU FP6. We thank Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Fondation pour la Recherche Médicale, Ville de Paris, Fondation BNP Paribas, and the European Research Council for financial support., We thank the members of the Microbes and Host Barriers Group for their support and Matteo Bonazzi and the personnel of the Imagopole Facility for their help and support. We thank Gerard Eberl for helpful discussion and advice., European Project: 35418,INTRAPATH, Equipe avenir Microorganismes et Barrières de l'Hôte, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]-Institut National de la Recherche Agronomique (INRA), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Institut Pasteur [Paris] (IP)

Subjects
MESH: Transcytosis, INVASION, MESH: Listeria monocytogenes, CAMPYLOBACTER-JEJUNI, MESH: Cadherins, Mice, Intestinal mucosa, Immunology and Allergy, Listeriosis, MESH: Animals, Intestinal Mucosa, IN-VIVO, 0303 health sciences, MESH: Exocytosis, Tight junction, SURFACE PROTEIN, Cell Polarity, respiratory system, Cadherins, Intestinal epithelium, 3. Good health, Cell biology, TRANSLOCATION, medicine.anatomical_structure, Transcytosis, MESH: Intestinal Mucosa, Goblet Cells, NEISSERIA-GONORRHOEAE, MESH: Cell Polarity, EPITHELIAL TIGHT JUNCTION, MESH: Mice, Transgenic, Immunology, Mice, Transgenic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, digestive system, Exocytosis, Article, Microbiology, Adherens junction, 03 medical and health sciences, MESH: Mice, Inbred C57BL, medicine, Animals, Humans, ESCHERICHIA-COLI K1, MESH: Mice, 030304 developmental biology, Goblet cell, Mucous Membrane, MESH: Humans, 030306 microbiology, Cadherin, MESH: Mucous Membrane, Listeria monocytogenes, Epithelium, Mice, Inbred C57BL, MESH: Listeriosis, MESH: Biomarkers, CACO-2 CELLS, MESH: Goblet Cells, Biomarkers, RAT SMALL-INTESTINE
Abstract

Listeria monocytogenes targets accessible E-cadherin expressed on mucus-producing goblet cells to invade the intestinal tissue., Listeria monocytogenes (Lm) is a foodborne pathogen that crosses the intestinal barrier upon interaction between its surface protein InlA and its species-specific host receptor E-cadherin (Ecad). Ecad, the key constituent of adherens junctions, is typically situated below tight junctions and therefore considered inaccessible from the intestinal lumen. In this study, we investigated how Lm specifically targets its receptor on intestinal villi and crosses the intestinal epithelium to disseminate systemically. We demonstrate that Ecad is luminally accessible around mucus-expelling goblet cells (GCs), around extruding enterocytes at the tip and lateral sides of villi, and in villus epithelial folds. We show that upon preferential adherence to accessible Ecad on GCs, Lm is internalized, rapidly transcytosed across the intestinal epithelium, and released in the lamina propria by exocytosis from where it disseminates systemically. Together, these results show that Lm exploits intrinsic tissue heterogeneity to access its receptor and reveal transcytosis as a novel and unanticipated pathway that is hijacked by Lm to breach the intestinal epithelium and cause systemic infection.

Published
2011

26. The surface protein HvgA mediates group B streptococcus hypervirulence and meningeal tropism in neonates

Author

Samuel Bellais, Huot Khun, Nicolas Dmytruk, Charlotte Mechler, Asmaa Tazi, Claire Poyart, Patrick Trieu-Cuot, Michel-Yves Mistou, Olivier Disson, Marc Lecuit, Shaynoor Dramsi, Abdelouhab Bouaboud, Isabelle Tardieux, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre national de Référence des Streptocoques (CNR), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Biologie des Bactéries Pathogènes à Gram-positif, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Histotechnologie et Pathologie, Institut Pasteur [Paris], Hôpital Louis Mourier - AP-HP [Colombes], Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Service des Maladies infectieuses et tropicales [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This work was supported by the Agence Nationale de la Recherche (ANR HyperVirGBS Project, ANR-08-MIE-015), Institut National de la Santé et de la Recherche Médicale, Institut Pasteur, Fondation pour la Recherche Médicale (FRM), Université Paris Descartes, the Institut de Veille Sanitaire, Programme Transversal de Recherche #190. S. Bellais was a recipient of a post-doctoral fellowship from the ANR-08-MIE-015 grant and O. Disson from FRM and Institut National de la Santé et de la Recherche Médicale., We are grateful to Alexandra Gruss for helpful discussion and critical reading of the manuscript. We thank Pierre-Olivier Couraud for providing HCMEC/D3 cells., ANR-08-MIEN-0015,HYPERVIRGBS,Rôle de la protéine Gbs2018C dans l'hypervirulence du clone ST-17 du Streptocoque du groupe B(2008), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Equipe avenir Microorganismes et Barrières de l'Hôte, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Hopital Louis Mourier - AP-HP [Colombes], and Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris]

Subjects
Male, MESH: Adhesins, Bacterial, [SDV]Life Sciences [q-bio], medicine.disease_cause, Bacterial Adhesion, MESH: Blood-Brain Barrier, Mice, Meninges, MESH: Streptococcal Infections, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immunology and Allergy, MESH: Animals, Intestinal Mucosa, MESH: Organ Specificity, 0303 health sciences, Streptococcus, MESH: Infant, Newborn, MESH: Infant, 3. Good health, Intestines, MESH: Meningitis, Bacterial, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Blood-Brain Barrier, Organ Specificity, MESH: Intestinal Mucosa, Female, Meningitis, MESH: Intestines, MESH: Bacterial Translocation, MESH: Meninges, Immunology, Virulence, Context (language use), Biology, Meningitis, Bacterial, Streptococcus agalactiae, Microbiology, Neonatal meningitis, 03 medical and health sciences, Streptococcal Infections, medicine, Animals, Humans, MESH: Bacterial Adhesion, Adhesins, Bacterial, MESH: Mice, Tropism, 030304 developmental biology, MESH: Humans, 030306 microbiology, Infant, Newborn, Brief Definitive Report, Infant, medicine.disease, MESH: Streptococcus agalactiae, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Male, Bacterial adhesin, Bacterial Translocation, MESH: HeLa Cells, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, HeLa Cells
Abstract

Lethal meningitis triggered by the hypervirulent group B streptococcus clone ST-17 is mediated by a novel surface protein called HvgA., Streptococcus agalactiae (group B streptococcus; GBS) is a normal constituent of the intestinal microflora and the major cause of human neonatal meningitis. A single clone, GBS ST-17, is strongly associated with a deadly form of the infection called late-onset disease (LOD), which is characterized by meningitis in infants after the first week of life. The pathophysiology of LOD remains poorly understood, but our epidemiological and histopathological results point to an oral route of infection. Here, we identify a novel ST-17–specific surface-anchored protein that we call hypervirulent GBS adhesin (HvgA), and demonstrate that its expression is required for GBS hypervirulence. GBS strains that express HvgA adhered more efficiently to intestinal epithelial cells, choroid plexus epithelial cells, and microvascular endothelial cells that constitute the blood–brain barrier (BBB), than did strains that do not express HvgA. Heterologous expression of HvgA in nonadhesive bacteria conferred the ability to adhere to intestinal barrier and BBB-constituting cells. In orally inoculated mice, HvgA was required for intestinal colonization and translocation across the intestinal barrier and the BBB, leading to meningitis. In conclusion, HvgA is a critical virulence trait of GBS in the neonatal context and stands as a promising target for the development of novel diagnostic and antibacterial strategies.

Published
2010

27. Human Listeriosis Caused by Listeria ivanovii

Author

Olivier Disson, Alban Le Monnier, Magdalena K. Bielecka, Olivier Join-Lambert, Christelle Guillet, Marie-France Mamzer-Bruneel, Patrick Berche, Mariela Scortti, Marc Lecuit, Alexandre Leclercq, Frédéric Méchaï, Olivier Lortholary, José A. Vázquez-Boland, Université Paris Descartes - Paris 5 (UPD5), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris], University of Edinburgh, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Institut National de la Santé et de la Recherche Médicale (INSERM), Universidad de León [León], M.L. received financial support from Assistance Publique–Hôpitaux de Paris, Université Paris Descartes, Institut Pasteur, Institut de Veille Sanitaire, and Institut National de la Santé et de la Recherche Médicale. J.V.-B. received Wellcome Trust program grant 074020., We thank Véronique Goulet for helpful discussions., and Institut Pasteur [Paris] (IP)

Subjects
Male, Epidemiology, [SDV]Life Sciences [q-bio], lcsh:Medicine, Human pathogen, MESH: Listeria, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Immunocompromised Host, Listeriosis, MESH: Animals, bacteria, MESH: Bacteremia, 0303 health sciences, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, biology, Goats, MESH: Paris, dispatch, Middle Aged, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Listeria ivanovii, gastroenteritis, Microbiology (medical), Paris, Listeria, kidney transplantation, Opportunistic Infections, MESH: Goats, Microbiology, lcsh:Infectious and parasitic diseases, Immunocompromised Host, 03 medical and health sciences, medicine, Animals, Humans, lcsh:RC109-216, bacteremia, 030304 developmental biology, MESH: Humans, 030306 microbiology, lcsh:R, MESH: Opportunistic Infections, biology.organism_classification, medicine.disease, Virology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Gastroenteritis, MESH: Male, MESH: Listeriosis, Bacteremia, Bacteria, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Two species of Listeria are pathogenic; L. monocytogenes infects humans and animals, and L. ivanovii has been considered to infect ruminants only. We report L. ivanovii–associated gastroenteritis and bacteremia in a man. This isolate was indistinguishable from prototypic ruminant strains. L. ivanovii is thus an enteric opportunistic human pathogen.The genus Listeria contains 2 pathogenic species, L. monocytogenes and L. ivanovii (1). They both invade host cells, replicate in the cytosol after phagosomal escape, and spread from cell to cell by polymerizing actin. These mechanisms correlate with the presence in each species of genetic determinants called the inlAB internalization locus, the LIPI-1 intracellular survival pathogenicity island, and the hpt intracellular growth locus (2). However, each species appears to infect different hosts: L. monocytogenes infects humans and ruminants, whereas L. ivanovii is thought to infect ruminants only (2). L. ivanovii have been previously isolated, although rarely, from infected humans, indicating pathogenic potential for humans (Table). We report a case of L. ivanovii infection in a man with a kidney transplant. The ecology of L. ivanovii suggests that the rarity of human listeriosis due to this species reflects not only host tropism factors but also the rare occurrence of this species in the environment, compared with L. monocytogenes.

Published
2010

28. Real-Time Observation of Listeria monocytogenes-Phagocyte Interactions in Living Zebrafish Larvae

Author

Philippe Herbomel, Pascale Cossart, Isabelle Bonne, Karima Kissa, Marc Lecuit, Jean-Pierre Levraud, Olivier Disson, Macrophages et Développement de l'Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Microscopie ultrastructurale (plate-forme), Institut Pasteur [Paris], Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and DIAKITE, andrée

Subjects
Phagocyte, Neutrophils, [SDV]Life Sciences [q-bio], Human pathogen, MESH: Neutrophils, MESH: Heat-Shock Proteins, medicine.disease_cause, MESH: Phagocytes, MESH: Listeria monocytogenes, MESH: Cadherins, Hemolysin Proteins, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Macrophage, MESH: Animals, Zebrafish, MESH: Bacterial Proteins, Heat-Shock Proteins, Phagosome, Phagocytes, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Bacterial Infections, Cadherins, 3. Good health, [SDV] Life Sciences [q-bio], Infectious Diseases, medicine.anatomical_structure, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Hemolysin Proteins, Larva, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Membrane Proteins, animal structures, Virulence Factors, Bacterial Toxins, Immunology, Virulence, Biology, Microbiology, 03 medical and health sciences, Bacterial Proteins, Listeria monocytogenes, medicine, Animals, MESH: Zebrafish, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, 030304 developmental biology, MESH: Virulence Factors, Innate immune system, 030306 microbiology, Macrophages, fungi, Membrane Proteins, MESH: Macrophages, biology.organism_classification, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Bacterial Toxins, Parasitology, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Larva, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

The zebrafish,Danio rerio, has become a popular vertebrate model for the study of infections, mainly because of its excellent optical accessibility at the embryonic and larval stages, when the innate immune system is already effective. We have thus tested the susceptibility of zebrafish larvae to the human pathogenListeria monocytogenes, a gram-positive, facultative, intracellular bacterium that is known to survive and multiply in professional phagocytes and that causes fatal meningitis and abortions. Intravenous injection of early zebrafish larvae resulted in a progressive and ultimately fatal infection. Blood-borneL. monocytogenesbacteria were quickly trapped and engulfed by macrophages, an event that, for the first time, could be captured in vivo and in real time. Granulocytes also participated in the innate immune response. As in mammals, bacteria could escape the macrophage phagosome in a listeriolysin-dependent manner and accessed the cytosol; this event was critical for bacterial virulence, as listeriolysin-deficient bacteria were completely avirulent. Actin comet tails and protrusions were observed, suggesting cell-to-cell spread; these phenomena also played a role in virulence in zebrafish larvae, asactA-deficient bacteria were attenuated. These results demonstrate the relevance of the genetically tractable and optically accessible zebrafish model for the study ofL. monocytogenespathogenesis and particularly for the dissection of its interactions with phagocytes in vivo, a key factor ofL. monocytogenesvirulence.

Published
2009

29. A Mouse Model for Chikungunya: Young Age and Inefficient Type-I Interferon Signaling Are Risk Factors for Severe Disease

Author

G. Barau, Fabrice Chrétien, Isabelle Schuffenecker, Olivier Disson, Thérèse Couderc, Alain Michault, Marc Lecuit, Matthew L. Albert, Florence Guivel-Benhassine, Nadège Cayet, Fernando Arenzana-Seisdedos, Clémentine Schilte, Philippe Desprès, Madly Brigitte, Yasmina Touret, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches et Développement / Stem Cells and Development, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de gynécologie-obstétrique [La réunion], Groupe Hospitalier Sud-CHR La réunion, Microscopie ultrastructurale (plate-forme), Institut Pasteur [Paris], Centre national de Référence et Centre Collaborateur de l'OMS Arbovirus (CNR-CCOMS), Interactions Moléculaires Flavivirus-Hôtes, Pathogénie Virale Moléculaire, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], This work received financial support from the Agence Nationale de la Recherche, Fondation pour la Recherche Médicale Inserm and Institut Pasteur (PTR 201). Marc Lecuit is the recipient of an Inserm interface contract., Vougny, Marie-Christine, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Interactions Bactéries-Cellules ( UIBC ), Institut National de la Recherche Agronomique ( INRA ) -Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cellules Souches et Développement, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Mondor de recherche biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Universitaire de La Réunion ( CHU La Réunion ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
Male, Disease, Virus Replication, medicine.disease_cause, Mice, 0302 clinical medicine, Homo (Human), Chlorocebus aethiops, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Chikungunya, Biology (General), Mice, Knockout, 0303 health sciences, Age Factors, virus diseases, Mus (Mouse), Viral Load, 3. Good health, Infectious Diseases, Liver, Viruses, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Chikungunya virus, Viral load, Research Article, Signal Transduction, medicine.drug, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, QH301-705.5, Longevity, 030231 tropical medicine, Immunology, Biology, Microbiology, Virus, 03 medical and health sciences, Cell Line, Tumor, Virology, Animals, Outbred Strains, Genetics, medicine, Animals, Humans, Alphavirus infection, Vero Cells, Molecular Biology, 030304 developmental biology, Alphavirus Infections, Infant, Newborn, RC581-607, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Animals, Newborn, Viral replication, Tissue tropism, Parasitology, Immunologic diseases. Allergy, Interferon type I
Abstract

Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection and the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent. Adult mice with a partially (IFN-α/βR+/−) or totally (IFN-α/βR−/−) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and inefficient type-I IFN signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates., Author Summary Chikungunya virus (CHIKV) is transmitted by mosquito bites. CHIKV has recently re-emerged and is responsible for a massive outbreak in the Indian Ocean region and India. It has also reached Italy, indicating that CHIKV has a great potential to spread globally. Infection from CHIKV typically induces a mild disease in humans, characterized by a flu-like syndrome associated with muscle and joint pain and rash. Cases of severe infection involving the central nervous system (CNS) have recently been described, notably in neonates. We have developed the first animal model for CHIKV infection and studied the pathophysiology of the resulting disease. We show here that mouse neonates are susceptible to CHIKV and neonatal disease severity is age-dependent. Adult mice with a partial or complete defect in type-I interferon pathway develop a mild or severe infection, respectively. In mice with a mild infection, CHIKV primarily targets muscle, joint and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to the CNS. Our work indicates that CHIKV-associated symptoms perfectly match viral tissue and cell tropisms, and demonstrate that the fibroblast is a prominent target cell of CHIKV. It also identifies the neonatal phase and inefficient type-I interferon signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates.

Published
2008

30. Impaired clearance of virus-infected hepatocytes in transgenic mice expressing the hepatitis C virus polyprotein

Author

Chantal Jacquet, Hervé Lerat, Michael Hahne, Solange Desagher, Olivier Disson, Delphine Haouzi, Stanley M. Lemon, Eric J. Kremer, Urszula Hibner, Kim Loesch, Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)

Subjects
Cytoplasm, Hepatitis C virus, Transgene, Adenoviridae Infections, Gene Expression, Apoptosis, Mice, Inbred Strains, Mice, Transgenic, Hepacivirus, Biology, medicine.disease_cause, Virus, 03 medical and health sciences, Mice, Viral Proteins, 0302 clinical medicine, Immune system, medicine, Cytotoxic T cell, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Transgenes, fas Receptor, 030304 developmental biology, mitochondrial permeability transition fas gene-mutations core protein oxidative stress hepatocellular-carcinoma mediated apoptosis death receptors immune-response t-cells pathway, Polyproteins, 0303 health sciences, Hepatology, Gastroenterology, Fas receptor, Virology, 3. Good health, Cell killing, Immunology, Antibody Formation, Hepatocytes, 030211 gastroenterology & hepatology, Carrier Proteins, BH3 Interacting Domain Death Agonist Protein, T-Lymphocytes, Cytotoxic
Abstract

International audience; Background & Aims: Multiple molecular mechanisms are likely to contribute to the establishment of persistent infection by hepatitis C virus (HCV). The aim of this work was to study the evasion of cell-mediated antiviral immune responses in transgenic mice with liver-targeted expression of the hepatitis C viral genome. These mice develop steatosis and hepatocellular carcinoma and constitute a murine model of chronic HCV infection. Methods: Mice of the FL-N/35 lineage were infected with replication-deficient adenoviral vectors encoding beta-galactosidase, and the persistence of infected cells was measured by histochemistry and enzymatic assays. Results: Hepatocytes from the HCV+ transgenic mice are deficient in eliminating an adenoviral infection, despite an apparently normal T-cell response. The defect in adenoviral clearance was associated with resistance of transgenic hepatocytes to apoptosis induced by Fas/ APO1/CD95 death receptor stimulation, a major pathway of cell killing by cytotoxic T lymphocytes. The attenuation of Fas-mediated apoptosis observed in the murine model was associated with a reduced abundance of Bid, a BH3-only member of the Bcl-2 family of apoptosis regulators. Conclusions: Our results suggest that viral evasion of cell-mediated immune responses leading to apoptotic death of hepatocytes may contribute to viral persistence. Such a mechanism might also contribute to the development of liver cancer in HCV.

Published
2004

31. Hepatocytes transgenic for the full hepatitis C virus open reading frame are resistant to fas-induced cell death

Author

Michael Hahne, Hervé Lerat, Olivier Disson, Urszula Hibner, Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)

Subjects
Genetically modified mouse, Programmed cell death, Indazoles, Hepatitis C virus, Transgene, Antineoplastic Agents, Mice, Transgenic, Hepacivirus, Biology, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Mice, Open Reading Frames, 03 medical and health sciences, 0302 clinical medicine, History and Philosophy of Science, Animals Antigens, medicine, Animals, CD95/pharmacology/*physiology Antineoplastic Agents/pharmacology Cell Death/drug effects/*physiology Cells, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, fas Receptor, Transgenic Mitochondria/physiology *Open Reading Frames Recombinant Proteins/pharmacology, Cells, Cultured, 030304 developmental biology, 0303 health sciences, Cell Death, General Neuroscience, Fas receptor, Virology, Molecular biology, Recombinant Proteins, Mitochondria, Open reading frame, Apoptosis, Cultured Hepacivirus/*genetics Hepatocytes/*cytology/drug effects Indazoles/pharmacology Mice Mice, Hepatocytes, 030211 gastroenterology & hepatology
Published
2002

32. Listeria monocytogenes faecal carriage is common and depends on the gut microbiota

Author

Lukas Hafner, Marc Garcia-Garcera, Christophe Burucoa, Marc Lecuit, Sophie H A Nusser, Maxime Pichon, Alexandra Moura, Frasca, Guillaume, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Institut Pasteur International Docotal Program - PASTEURDOC - - H20202015-10-01 - 2020-10-01 - 665807 - VALID, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Pharmacologie des anti-infectieux (PHAR), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)-Université Paris Cité (UPCité), Université de Lausanne = University of Lausanne (UNIL), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), L.H. is supported by the Pasteur-Paris University (PPU) International Ph.D. Programme, funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 665807, the ‘Ecole Doctorale FIRE-Programme Bettencourt’ of the CRI Paris and the Fondation Pasteur Suisse. M.L. laboratory is funded by Institut Pasteur, Inserm, the European Research Council and Laboratoire d’Excellence Integrative Biology of Emerging Infectious Diseases. M.L. is a member of Institut Universitaire de France., We thank Hélène Bracq-Dieye for technical help, Georges Michel Haustant, Cédric Fund, Elodie Turc, Laure Lemée, Biomics Platform, C2RT, Institut Pasteur, Paris, France, supported by France Génomique (ANR-10-INBS-09-09) and IBISA for 16S sequencing, Auguste Fourneau and Amandine Brunet for PCR assays and Sandrine Isaac, Henrik Salje and Olivier Disson for critical reading., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 665807,H2020,H2020-MSCA-COFUND-2014,PASTEURDOC(2015), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université de Lausanne (UNIL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), and Centre National de Référence Listeria - National Reference Center Listeria (CNR)

Subjects
DNA, Bacterial, Male, Science, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Virulence, Datasets as Topic, Gut flora, medicine.disease_cause, General Biochemistry, Genetics and Molecular Biology, Article, Microbiology, 03 medical and health sciences, Feces, Mice, fluids and secretions, Listeria monocytogenes, Abundance (ecology), RNA, Ribosomal, 16S, medicine, Animals, Humans, Phylogeny, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, 030306 microbiology, Inoculation, General Chemistry, Bacterial pathogenesis, biology.organism_classification, 16S ribosomal RNA, Gastrointestinal Microbiome, [SDV] Life Sciences [q-bio], Disease Models, Animal, Metagenomics, Carrier State, Listeria
Abstract

Listeria genus comprises two pathogenic species, L. monocytogenes (Lm) and L. ivanovii, and non-pathogenic species. All can thrive as saprophytes, whereas only pathogenic species cause systemic infections. Identifying Listeria species’ respective biotopes is critical to understand the ecological contribution of Listeria virulence. In order to investigate the prevalence and abundance of Listeria species in various sources, we retrieved and analyzed 16S rRNA datasets from MG-RAST metagenomic database. 26% of datasets contain Listeria sensu stricto sequences, and Lm is the most prevalent species, most abundant in soil and host-associated environments, including 5% of human stools. Lm is also detected in 10% of human stool samples from an independent cohort of 900 healthy asymptomatic donors. A specific microbiota signature is associated with Lm faecal carriage, both in humans and experimentally inoculated mice, in which it precedes Lm faecal carriage. These results indicate that Lm faecal carriage is common and depends on the gut microbiota, and suggest that Lm faecal carriage is a crucial yet overlooked consequence of its virulence., Here, the authors show that Listeria monocytogenes faecal carriage is common in healthy asymptomatic individuals and, together with mouse studies, they associate carriage with a specific microbiome signature.

Published
2021

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