Search

Your search keyword '"Camille Blériot"' showing total 33 results
Start Over Author "Camille Blériot"
33 results on '"Camille Blériot"'

1. Proteomic analysis of ascitic extracellular vesicles describes tumour microenvironment and predicts patient survival in ovarian cancer

Author

Anna Vyhlídalová Kotrbová, Kristína Gömöryová, Antónia Mikulová, Hana Plešingerová, Stanislava Sladeček, Marek Kravec, Šárka Hrachovinová, David Potěšil, Garett Dunsmore, Camille Blériot, Mathilde Bied, Jan Kotouček, Markéta Bednaříková, Jitka Hausnerová, Luboš Minář, Igor Crha, Michal Felsinger, Zbyněk Zdráhal, Florent Ginhoux, Vít Weinberger, Vitězslav Bryja, and Vendula Pospíchalová

Subjects
ascites, extracellular vesicles (EV), fallopian tube and peritoneum (HGSC), high‐grade serous carcinoma of the ovary, macrophage, ovarian cancer (OC), Cytology, QH573-671
Abstract

Abstract High‐grade serous carcinoma of the ovary, fallopian tube and peritoneum (HGSC), the most common type of ovarian cancer, ranks among the deadliest malignancies. Many HGSC patients have excess fluid in the peritoneum called ascites. Ascites is a tumour microenvironment (TME) containing various cells, proteins and extracellular vesicles (EVs). We isolated EVs from patients’ ascites by orthogonal methods and analyzed them by mass spectrometry. We identified not only a set of ‘core ascitic EV‐associated proteins’ but also defined their subset unique to HGSC ascites. Using single‐cell RNA sequencing data, we mapped the origin of HGSC‐specific EVs to different types of cells present in ascites. Surprisingly, EVs did not come predominantly from tumour cells but from non‐malignant cell types such as macrophages and fibroblasts. Flow cytometry of ascitic cells in combination with analysis of EV protein composition in matched samples showed that analysis of cell type‐specific EV markers in HGSC has more substantial prognostic potential than analysis of ascitic cells. To conclude, we provide evidence that proteomic analysis of EVs can define the cellular composition of HGSC TME. This finding opens numerous avenues both for a better understanding of EV's role in tumour promotion/prevention and for improved HGSC diagnostics.

Published
2024
Full Text
View/download PDF

2. Macrophages and the development and progression of non-alcoholic fatty liver disease

Author

Bader Alabdulaali, Fatema Al-rashed, Mohammed Al-Onaizi, Anwar Kandari, Joanna Razafiarison, Dorothy Tonui, Michayla R. Williams, Camille Blériot, Rasheed Ahmad, and Fawaz Alzaid

Subjects
non-alcoholic fatty liver disease, fibrosis, macrophages, inflammation, Kupffer cells, Immunologic diseases. Allergy, RC581-607
Abstract

The liver is the site of first pass metabolism, detoxifying and metabolizing blood arriving from the hepatic portal vein and hepatic artery. It is made up of multiple cell types, including macrophages. These are either bona fide tissue-resident Kupffer cells (KC) of embryonic origin, or differentiated from circulating monocytes. KCs are the primary immune cells populating the liver under steady state. Liver macrophages interact with hepatocytes, hepatic stellate cells, and liver sinusoidal endothelial cells to maintain homeostasis, however they are also key contributors to disease progression. Generally tolerogenic, they physiologically phagocytose foreign particles and debris from portal circulation and participate in red blood cell clearance. However as immune cells, they retain the capacity to raise an alarm to recruit other immune cells. Their aberrant function leads to the development of non-alcoholic fatty liver disease (NAFLD). NAFLD refers to a spectrum of conditions ranging from benign steatosis of the liver to steatohepatitis and cirrhosis. In NAFLD, the multiple hit hypothesis proposes that simultaneous influences from the gut and adipose tissue (AT) generate hepatic fat deposition and that inflammation plays a key role in disease progression. KCs initiate the inflammatory response as resident immune effectors, they signal to neighbouring cells and recruit monocytes that differentiated into recruited macrophages in situ. Recruited macrophages are central to amplifying the inflammatory response and causing progression of NAFLD to its fibro-inflammatory stages. Given their phagocytic capacity and their being instrumental in maintaining tissue homeostasis, KCs and recruited macrophages are fast-becoming target cell types for therapeutic intervention. We review the literature in the field on the roles of these cells in the development and progression of NAFLD, the characteristics of patients with NAFLD, animal models used in research, as well as the emerging questions. These include the gut-liver-brain axis, which when disrupted can contribute to decline in function, and a discussion on therapeutic strategies that act on the macrophage-inflammatory axis.

Published
2023
Full Text
View/download PDF

4. Isolation of mouse Kupffer cells for phenotypic and functional studies

Author

Francesco Andreata, Camille Blériot, Pietro Di Lucia, Giorgia De Simone, Valeria Fumagalli, Xenia Ficht, Cristian Gabriel Beccaria, Mirela Kuka, Florent Ginhoux, and Matteo Iannacone

Subjects
Cell culture, Cell isolation, Flow Cytometry/Mass Cytometry, Immunology, Single Cell, Science (General), Q1-390
Abstract

Summary: Here, we provide detailed protocols for the isolation of mouse Kupffer cells – the liver-resident macrophages – for phenotypic (e.g., via flow cytometry, mass cytometry, or RNA-sequencing) analyses or for functional experiments involving cell culture. The procedures presented can be adapted for the isolation of other hepatic cell populations.For complete details on the use and execution of this protocol, please refer to De Simone et al. (2021).

Published
2021
Full Text
View/download PDF

5. Non-genetic Heterogeneity of Macrophages in Diseases—A Medical Perspective

Author

Grégoire Gessain, Camille Blériot, and Florent Ginhoux

Subjects
macrophage, monocyte, heterogeneity, human diseases, ontogeny, tissue-resident, Biology (General), QH301-705.5
Abstract

Macrophages are sessile immune cells with a high functional plasticity. Initially considered as a uniform population of phagocytic scavengers, it is now widely accepted that these cells also assume developmental and metabolic functions specific of their tissue of residence. Hence, the paradigm is shifting while our comprehension of macrophage heterogeneity improves. Accordingly, exploiting this intrinsic versatility appears more and more promising for the establishment of innovative therapeutic strategies. Nevertheless, identifying relevant therapeutic targets remains a considerable challenge. Herein, we discuss various features of macrophage heterogeneity in five main categories of human diseases: infectious, inflammatory, metabolic, age-related, and neoplastic disorders. We summarize the current understanding of how macrophage heterogeneity may impact the pathogenesis of these diseases and propose a comprehensive overview with the aim to help in establishing future macrophage-targeted therapies.

Published
2020
Full Text
View/download PDF

6. Understanding the Heterogeneity of Resident Liver Macrophages

Author

Camille Blériot and Florent Ginhoux

Subjects
liver, macrophage, heterogeneity, single cell RNA sequencing, monocyte, Immunologic diseases. Allergy, RC581-607
Abstract

Resident tissue macrophages (RTMs) are cells with a high functional plasticity assuming pleiotropic roles in their tissue of residence, from clearance of dead cells and metabolic sensing in steady state to cytokine production and tissue repair during inflammation. The liver has long been considered as only populated by Kupffer cells (KCs), a macrophage population assumed to be in charge of all of these functions. However, we know now that KCs are not the only macrophage population in the liver, that recently was shown to contain also capsular macrophages, monocyte-derived macrophages as well as recruited peritoneal macrophages inherited from previous inflammatory events. These macrophages exhibit different origins, time of establishing residence and locations in the liver, with both ontogenical and environmental factors shaping their identity and functions. Furthermore, liver macrophages reside in a complex environment with a pronounced metabolic zonation. Here, we briefly discuss how these intrinsic and extrinsic factors influence macrophage biology and liver physiology in general. We notably focus on how the recent advances of single cell transcriptomic approaches are changing our understanding of liver macrophages and diseases.

Published
2019
Full Text
View/download PDF

7. Inflammatory and immune etiology of type 2 diabetes

Author

Camille Blériot, Élise Dalmas, Florent Ginhoux, and Nicolas Venteclef

Subjects
Immunology, Immunology and Allergy
Abstract

Type 2 diabetes (T2D) represents a global threat affecting millions of patients worldwide. However, its causes remain incompletely dissected and we lack the tools to predict which individuals will develop T2D. Although there is a clear proven clinical association of T2D with metabolic disorders such as obesity and nonalcoholic fatty liver disease (NAFLD), the existence of a significant number of nondiabetic obese subjects suggests yet-uncovered features of such relationships. Here, we propose that a significant proportion of individuals may harbor an immune profile that renders them susceptible to developing T2D. We note the heterogeneity of circulating monocytes and tissue macrophages in organs that are key to metabolic disorders such as liver, white adipose tissue (WAT), and endocrine pancreas, as well as their contribution to T2D genesis.

Published
2023

10. Response to contamination of isolated mouse Kupffer cells with liver sinusoidal endothelial cells

Author

Matteo Iannacone, Camille Blériot, Francesco Andreata, Xenia Ficht, Chiara Laura, Jose M. Garcia-Manteiga, Stefan Uderhardt, Florent Ginhoux, Iannacone, M, Blériot, C, Andreata, F, Ficht, X, Laura, C, Garcia-Manteiga, J, Uderhardt, S, and Ginhoux, F

Subjects
Mice, Infectious Diseases, Liver, MED/04 - PATOLOGIA GENERALE, Immunology, Hepatocytes, Animals, Endothelial Cells, Immunology and Allergy, Kupffer cells, Mononuclear Phagocyte System
Published
2022

11. Tissue-resident ductal macrophages survey the mammary epithelium and facilitate tissue remodelling

Author

Jane E. Visvader, Scott N. Mueller, Florent Ginhoux, Camille Blériot, Geoffrey J. Lindeman, Caleb A. Dawson, Anne C. Rios, Bhupinder Pal, Zhaoyuan Liu, François Vaillant, Luke C. Gandolfo, and Gordon K. Smyth

Subjects
Population, Biology, Epithelium, Monocytes, Flow cytometry, Mice, 03 medical and health sciences, Mammary Glands, Animal, 0302 clinical medicine, Immune system, Phagocytosis, Pregnancy, medicine, Animals, Lactation, Involution (medicine), education, Cell Proliferation, 030304 developmental biology, 0303 health sciences, education.field_of_study, medicine.diagnostic_test, Macrophages, Epithelial Cells, Cell Biology, Embryonic stem cell, Cell biology, Mice, Inbred C57BL, medicine.anatomical_structure, Mammary Epithelium, 030220 oncology & carcinogenesis, Female, Stem cell
Abstract

Macrophages are diverse immune cells that reside in all tissues. Although macrophages have been implicated in mammary-gland function, their diversity has not been fully addressed. By exploiting high-resolution three-dimensional imaging and flow cytometry, we identified a unique population of tissue-resident ductal macrophages that form a contiguous network between the luminal and basal layers of the epithelial tree throughout postnatal development. Ductal macrophages are long lived and constantly survey the epithelium through dendrite movement, revealed via advanced intravital imaging. Although initially originating from embryonic precursors, ductal macrophages derive from circulating monocytes as they expand during puberty. Moreover, they undergo proliferation in pregnancy to maintain complete coverage of the epithelium in lactation, when they are poised to phagocytose milk-producing cells post-lactation and facilitate remodelling. Interestingly, ductal macrophages strongly resemble mammary tumour macrophages and form a network that pervades the tumour. Thus, the mammary epithelium programs specialized resident macrophages in both physiological and tumorigenic contexts.

Published
2020

12. A subset of Kupffer cells regulates metabolism through the expression of CD36

Author

Guochen Wan, Nicholas Ang, Shanshan W. Howland, Svetoslav Chakarov, Evan W. Newell, Gregoire Gessain, Wan Ting Kong, Cecilia Morgantini, Olivier N. F. Cexus, Bernett Lee, Zhaoyuan Liu, Xenia Ficht, Ping Chen, Giorgia De Simone, Emelie Barreby, Josephine Lum, Nicolas Venteclef, Francesco Andreata, Ahad Khalilnezhad, Myriam Aouadi, Jinmiao Chen, Connie Xu, Xiaomeng Zhang, Ivy Low, Foo Shihui, Garett Dunsmore, Anis Larbi, Laurent Yvan-Charvet, Camille Blériot, Wei Guo, Rhea Pai, Muhammad Faris Bin Mohd Kairi, Benoit Malleret, Radoslaw M. Sobota, Wint Wint Phoo, Florent Ginhoux, Lai Guan Ng, Valerio Azzimato, Marc Bajénoff, Raphaelle Ballaire, Matteo Iannacone, Valeria Fumagalli, Ankur Sharma, Akhila Balachander, Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Karolinska Institute, Institut Gustave Roussy (IGR), Immunologie anti-tumorale et immunothérapie des cancers (ITIC), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Inovarion, IRCCS San Raffaele Scientific Institute [Milan, Italie], Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Equipe Electronique - Laboratoire GREYC - UMR6072, Groupe de Recherche en Informatique, Image et Instrumentation de Caen (GREYC), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Karolinska Institutet [Stockholm], Shangaï Jiao Tong University [Shangaï], Genome Institute of Singapore (GIS), National University of Singapore (NUS), University of Surrey (UNIS), Agency for science, technology and research [Singapore] (A*STAR), Aix Marseille Université (AMU), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Immunité et métabolisme dans le diabète = IMmunity and MEtabolism in DIABetes [CRC] (IMMEDIAB Lab), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), Shanghai Jiao Tong University [Shanghai], Clinical Research Center, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden, Karolinska Institutet [Stockholm]-Karolinska University Hospital [Stockholm], Inserm Avenir Group, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), INSERM U1015, Unit of Immunology, Rheumatology, Allergy and Rare diseases, Milan (IRCCS San Raffaele Scientific Institute), E-institute of Shanghai University Immunology Division, Shanghai University, University of Surrey, - Biosciences and Medicine, Faculty of Health and Medical Sciences, Guildford, SingMass National Laboratory - Singapore, Bleriot, C., Barreby, E., Dunsmore, G., Ballaire, R., Chakarov, S., Ficht, X., De Simone, G., Andreata, F., Fumagalli, V., Guo, W., Wan, G., Gessain, G., Khalilnezhad, A., Zhang, X. M., Ang, N., Chen, P., Morgantini, C., Azzimato, V., Kong, W. T., Liu, Z., Pai, R., Lum, J., Shihui, F., Low, I., Xu, C., Malleret, B., Kairi, M. F. M., Balachander, A., Cexus, O., Larbi, A., Lee, B., Newell, E. W., Ng, L. G., Phoo, W. W., Sobota, R. M., Sharma, A., Howland, S. W., Chen, J., Bajenoff, M., Yvan-Charvet, L., Venteclef, N., Iannacone, M., Aouadi, M., Ginhoux, F., Bleriot, C, Barreby, E, Dunsmore, G, Ballaire, R, Chakarov, S, Ficht, X, De Simone, G, Andreata, F, Fumagalli, V, Guo, W, Wan, G, Gessain, G, Khalilnezhad, A, Zhang, X, Ang, N, Chen, P, Morgantini, C, Azzimato, V, Kong, W, Liu, Z, Pai, R, Lum, J, Shihui, F, Low, I, Xu, C, Malleret, B, Kairi, M, Balachander, A, Cexus, O, Larbi, A, Lee, B, Newell, E, Ng, L, Phoo, W, Sobota, R, Sharma, A, Howland, S, Chen, J, Bajenoff, M, Yvan-Charvet, L, Venteclef, N, Iannacone, M, Aouadi, M, Ginhoux, F, and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)

Subjects
CD36 Antigens, Kupffer Cells, CD36, [SDV]Life Sciences [q-bio], Immunology, Population, Kupffer cell, macrophage, liver, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Immune system, scRNA-seq, medicine, Immunology and Allergy, Gene silencing, Macrophage, Animals, Obesity, education, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, education.field_of_study, biology, Fatty acid metabolism, high fat diet, medicine.disease, Phenotype, Cell biology, macrophages, single cell, Oxidative Stress, Infectious Diseases, chemistry, CD206, Liver, 030220 oncology & carcinogenesis, biology.protein, Steatosis, heterogeneity, metabolism
Abstract

Tissue macrophages are immune cells whose phenotypes and functions are dictated by origin and niches. However, tissues are complex environments, and macrophage heterogeneity within the same organ has been overlooked so far. Here, we used high-dimensional approaches to characterize macrophage populations in the murine liver. We identified two distinct populations among embryonically derived Kupffer cells (KCs) sharing a core signature while differentially expressing numerous genes and proteins: a major CD206loESAM– population (KC1) and a minor CD206hiESAM+ population (KC2). KC2 expressed genes involved in metabolic processes, including fatty acid metabolism both in steady-state and in diet-induced obesity and hepatic steatosis. Functional characterization by depletion of KC2 or targeted silencing of the fatty acid transporter Cd36 highlighted a crucial contribution of KC2 in the liver oxidative stress associated with obesity. In summary, our study reveals that KCs are more heterogeneous than anticipated, notably describing a subpopulation wired with metabolic functions.

Published
2021

13. Isolation of mouse Kupffer cells for phenotypic and functional studies

Author

Mirela Kuka, Cristian Gabriel Beccaria, Matteo Iannacone, Xenia Ficht, Francesco Andreata, Valeria Fumagalli, Camille Blériot, Florent Ginhoux, Pietro Di Lucia, Giorgia De Simone, Andreata, F, Blériot, C, Di Lucia, P, De Simone, G, Fumagalli, V, Ficht, X, Beccaria, C, Kuka, M, Ginhoux, F, Iannacone, M, Andreata, Francesco, Blériot, Camille, Di Lucia, Pietro, De Simone, Giorgia, Fumagalli, Valeria, Ficht, Xenia, Beccaria, Cristian Gabriel, Kuka, Mirela, Ginhoux, Florent, and Iannacone, Matteo

Subjects
Science (General), Kupffer Cells, Immunology, Cell Culture Techniques, Single Cell, Biology, General Biochemistry, Genetics and Molecular Biology, Flow cytometry, Q1-390, Mice, Protocol, medicine, Animals, Mass cytometry, Cell isolation, Functional studies, Flow Cytometry/Mass Cytometry, General Immunology and Microbiology, medicine.diagnostic_test, General Neuroscience, Flow Cytometry, Isolation (microbiology), Phenotype, Cell biology, Cell culture, Hepatic stellate cell
Abstract

Summary Here, we provide detailed protocols for the isolation of mouse Kupffer cells – the liver-resident macrophages – for phenotypic (e.g., via flow cytometry, mass cytometry, or RNA-sequencing) analyses or for functional experiments involving cell culture. The procedures presented can be adapted for the isolation of other hepatic cell populations. For complete details on the use and execution of this protocol, please refer to De Simone et al. (2021)., Graphical abstract, Highlights • Protocol for Kupffer cell (KC) isolation • Suitable for the simultaneous isolation of other hepatic cell populations • Isolated KCs are suitable for phenotypic and functional analyses • We provide critical tips for cell processing and FACS-based sorting, Here, we provide detailed protocols for the isolation of mouse Kupffer cells – the liver-resident macrophages – for phenotypic (e.g., via flow cytometry, mass cytometry or RNA-sequencing) analyses or for functional experiments involving cell culture. The procedures presented can be adapted for the isolation of other hepatic cell populations.

Published
2021

14. Non-genetic Heterogeneity of Macrophages in Diseases—A Medical Perspective

Author

Florent Ginhoux, Grégoire Gessain, and Camille Blériot

Subjects
human diseases, Population, Inflammation, Computational biology, Review, macrophage, Biology, Cell and Developmental Biology, Immune system, medicine, Macrophage, education, tissue-resident, lcsh:QH301-705.5, education.field_of_study, Genetic heterogeneity, Monocyte, Cell Biology, medicine.anatomical_structure, ontogeny, lcsh:Biology (General), inflammation, Structural plasticity, monocyte, medicine.symptom, heterogeneity, Developmental Biology
Abstract

Macrophages are sessile immune cells with a high functional plasticity. Initially considered as a uniform population of phagocytic scavengers, it is now widely accepted that these cells also assume developmental and metabolic functions specific of their tissue of residence. Hence, the paradigm is shifting while our comprehension of macrophage heterogeneity improves. Accordingly, exploiting this intrinsic versatility appears more and more promising for the establishment of innovative therapeutic strategies. Nevertheless, identifying relevant therapeutic targets remains a considerable challenge. Herein, we discuss various features of macrophage heterogeneity in five main categories of human diseases: infectious, inflammatory, metabolic, age-related, and neoplastic disorders. We summarize the current understanding of how macrophage heterogeneity may impact the pathogenesis of these diseases and propose a comprehensive overview with the aim to help in establishing future macrophage-targeted therapies.

Published
2020

15. Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease

Author

Shabnam Khalilnezhad, Lisa Derosa, Charles-Antoine Dutertre, John Kit Chung Tam, Salvatore Albani, Florent Ginhoux, Pierce K. H. Chow, Wan Ting Kong, Agathe Dubuisson, Aymeric Silvin, Tony Kiat Hon Lim, Jinmiao Chen, Jerry Kok Yen Chan, Antonio Bertoletti, Ahmed Ibrahim Samir Khalil, Suny Z. Wu, Evelyn Halitzki, Regina Men Men Wong, Marion Chevrier, Ankur Sharma, Kevin Mulder, Laurence Zitvogel, Rhea Pai, Camille Blériot, Alexander Swarbrick, Garett Dunsmore, Daniel L. Roden, Cécile Piot, Xiao Meng Zhang, Amit Ashok Patel, Ghamdan Al-Eryani, and Sergio Erdal Irac

Subjects
Liver Cirrhosis, Regulatory T cell, Immunology, Cell, Gene Expression, Inflammation, L-Amino Acid Oxidase, T-Lymphocytes, Regulatory, Monocytes, Arthritis, Rheumatoid, Interferon-gamma, Interferon, PD-L1, Neoplasms, RNA, Small Cytoplasmic, Tumor-Associated Macrophages, medicine, Immunology and Allergy, Macrophage, Humans, CD40, biology, Gene Expression Profiling, Macrophages, RNA, COVID-19, Dendritic Cells, Cell biology, Infectious Diseases, medicine.anatomical_structure, biology.protein, medicine.symptom, Single-Cell Analysis, Transcriptome, medicine.drug
Abstract

Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumor-associated macrophage populations. In particular, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumor periphery in a T cell-dependent manner via interferon-γ (IFN-γ) and CD40/CD40L-induced maturation from IFN-primed monocytes. IL4I1_Macs exhibited immunosuppressive characteristics through tryptophan degradation and promoted the entry of regulatory T cell into tumors. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.

Published
2020

16. Kupffer Cell Characterization by Mass Cytometry

Author

Camille, Blériot, Shamin, Li, Muhammad Faris Bin Mohd, Kairi, Evan, Newell, and Florent, Ginhoux

Subjects
Mice, Liver, Kupffer Cells, Macrophages, Animals, Flow Cytometry
Abstract

Kupffer cells are the liver-resident macrophages lining the sinusoids and are mostly known for their role of scavengers, as crucial keepers of organ integrity. But due to the many fundamental functions of the liver notably linked to detoxication, metabolism, protein synthesis, or immunology, Kupffer cells are exposed to a dynamic environment and constantly adapt themselves by modulating their gene and protein expressions. In this context, the characterization of these cells at steady-state and upon challenges may be limited by the classical microscopy or flow cytometry which allow for the use of only few selected markers. On the other end, transcriptomic approach, although being very powerful, can be costly and time-consuming. So mass cytometry offers a good compromise, allowing for the monitoring of a representative set of markers (up to 40) in a simple experiment. Herein, we describe a straightforward experimental and analysis workflow for Kupffer cell characterization by mass cytometry.

Published
2020

17. Determinants of Resident Tissue Macrophage Identity and Function

Author

Svetoslav Chakarov, Camille Blériot, and Florent Ginhoux

Subjects
0301 basic medicine, Immunology, Niche, Cell Plasticity, Inflammation, Context (language use), Biology, Monocytes, 03 medical and health sciences, 0302 clinical medicine, medicine, Immunology and Allergy, Macrophage, Animals, Humans, Macrophages, Macrophage Activation, Embryonic stem cell, Phenotype, 030104 developmental biology, Infectious Diseases, Cellular Microenvironment, Organ Specificity, 030220 oncology & carcinogenesis, Disease Susceptibility, medicine.symptom, Adaptation, Neuroscience, Function (biology), Biomarkers
Abstract

Resident tissue macrophages (RTMs) have a broad spectrum of immune- and non-immune-related tissue-supporting activities. The roots of this heterogeneity and versatility are only beginning to be understood. Here, we propose a conceptual framework for considering the RTM heterogeneity that organizes the factors shaping RTM identity within four cardinal points: (1) ontogeny and the view that adult RTM populations comprise a defined mixture of cells that arise from either embryonic precursors or adult monocytes; (2) local factors unique to the niche of residence, evolving during development and aging; (3) inflammation status; and (4) the cumulative effect of time spent in a specific tissue that contributes to the resilient adaptation of macrophages to their dynamic environment. We review recent findings within this context and discuss the technological advances that are revolutionizing the study of macrophage biology.

Published
2020

18. Adipose Tissue Vasculature Facilitates Immune Activation of Macrophages Via the CD200-CD200R Axis

Author

Mireille Cormont, Kirsty L. Spalding, Mikael Rydén, Qian Li, Camille Blériot, André Sulen, Emelie Barreby, Erik Näslund, Valerio Azzimato, April S. Caravaca, Connie Xu, Jurga Laurencikiene, Jennifer Jager, Cecilia Morgantini, Ana Domingos, Xidan Li, Florent Ginhoux, Laura Levi, Sinem Ozcan, Francisco Verdeguer, Myriam Aouadi, Jerome Gilleron, Inês Mahú, and Peder S. Olofsson

Subjects
education.field_of_study, Mediator, Systems biology, Adipose tissue macrophages, Population, Gene silencing, Adipose tissue, Biology, education, Reprogramming, Immune activation, Cell biology
Abstract

The activation of adipose tissue macrophages (ATMs) in obesity is a key mediator of metabolic complications. Therefore, deciphering the cellular and molecular mechanisms initiating ATM activation could reveal regulatory pathways important to prevent obesity‐associated metabolic disorders. While stressed or dying adipocytes have been described as the source of factors activating ATMs, herein we discovered that endothelial cells directly communicate with a distinct population of ATMs to induce their transcriptional reprogramming in response to obesity in mice and humans. CD200R expressed by these perivascular ATMs regulated the acquisition of unique properties shaped by the obese adipose tissue vasculature. Systems biology and ATM-specific silencing in obese mice revealed a unique downstream signaling whereby CD200R act as a rheostat controlling multiple functions of ATMs. Together, these studies provide evidence for a CD200-CD200R axis triggering the reprogramming of ATMs by endothelial cells in obesity.

Published
2020

19. Kupffer Cell Characterization by Mass Cytometry

Author

Florent Ginhoux, Shamin Li, Camille Blériot, Muhammad Faris Bin Mohd Kairi, and Evan W. Newell

Subjects
0301 basic medicine, medicine.diagnostic_test, Chemistry, Kupffer cell, Context (language use), Detoxication, Flow cytometry, Cell biology, Transcriptome, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, medicine, Protein biosynthesis, Mass cytometry
Abstract

Kupffer cells are the liver-resident macrophages lining the sinusoids and are mostly known for their role of scavengers, as crucial keepers of organ integrity. But due to the many fundamental functions of the liver notably linked to detoxication, metabolism, protein synthesis, or immunology, Kupffer cells are exposed to a dynamic environment and constantly adapt themselves by modulating their gene and protein expressions. In this context, the characterization of these cells at steady-state and upon challenges may be limited by the classical microscopy or flow cytometry which allow for the use of only few selected markers. On the other end, transcriptomic approach, although being very powerful, can be costly and time-consuming. So mass cytometry offers a good compromise, allowing for the monitoring of a representative set of markers (up to 40) in a simple experiment. Herein, we describe a straightforward experimental and analysis workflow for Kupffer cell characterization by mass cytometry.

Published
2020

20. Identification of a Kupffer cell subset capable of reverting the T cell dysfunction induced by hepatocellular priming

Author

Xenia Ficht, Marc Bajénoff, Alexandre P. Benechet, Matteo Iannacone, Federica Moalli, Svetoslav Chakarov, José M. Garcia-Manteiga, Paola Zordan, Pietro Di Lucia, Francesco Andreata, Chiara Laura, Luca G. Guidotti, Marta Mainetti, Giorgia De Simone, Camille Blériot, Elisa Bono, Gioia Ambrosi, Leonardo Giustini, Valeria Fumagalli, Stefano Gilotto, Micol Ravà, Federico F. De Ponti, Florent Ginhoux, Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), IRCCS San Raffaele Scientific Institute [Milan, Italie], Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), School of Medicine [Shanghai Jiaotong University], Shanghai Jiaotong University, Agency for science, technology and research [Singapore] (A*STAR), De Simone, G., Andreata, F., Bleriot, C., Fumagalli, V., Laura, C., Garcia-Manteiga, J. M., Di Lucia, P., Gilotto, S., Ficht, X., De Ponti, F. F., Bono, E. B., Giustini, L., Ambrosi, G., Mainetti, M., Zordan, P., Benechet, A. P., Rava, M., Chakarov, S., Moalli, F., Bajenoff, M., Guidotti, L. G., Ginhoux, F., Iannacone, M., De Simone, G, Andreata, F, Bleriot, C, Fumagalli, V, Laura, C, Garcia-Manteiga, J, Di Lucia, P, Gilotto, S, Ficht, X, De Ponti, F, Bono, E, Giustini, L, Ambrosi, G, Mainetti, M, Zordan, P, Benechet, A, Rava, M, Chakarov, S, Moalli, F, Bajenoff, M, Guidotti, L, Ginhoux, F, Iannacone, M, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), and Bajenoff, Marc

Subjects
[SDV]Life Sciences [q-bio], hepatitis B viru, Priming (immunology), CD8-Positive T-Lymphocytes, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, ACTIVATION, Mice, 0302 clinical medicine, Immunology and Allergy, Cytotoxic T cell, Kupffer cells, T cell dysfunction, RNA-SEQ, Antigen Presentation, 0303 health sciences, tolerance, CD8(+) T cells, Effector, MED/04 - PATOLOGIA GENERALE, Kupffer cell, imaging, Hepatitis B, single cell, 3. Good health, Infectious Diseases, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, CD8+ T cell, medicine.drug, EXPRESSION, Interleukin 2, Kupffer Cells, Immunology, FATE, T cells, Mice, Transgenic, Biology, +, liver, Major histocompatibility complex, DENDRITIC CELLS, Article, 03 medical and health sciences, Cross-Priming, Antigen, scRNA-seq, Immune Tolerance, medicine, Animals, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, 030304 developmental biology, IL-2, Biology and Life Sciences, CD8, CROSS, Cancer research, biology.protein, CD8+ T cells, Interleukin-2, interleukin-2, hepatitis B virus, RESPONSES
Abstract

Summary Kupffer cells (KCs) are highly abundant, intravascular, liver-resident macrophages known for their scavenger and phagocytic functions. KCs can also present antigens to CD8+ T cells and promote either tolerance or effector differentiation, but the mechanisms underlying these discrepant outcomes are poorly understood. Here, we used a mouse model of hepatitis B virus (HBV) infection, in which HBV-specific naive CD8+ T cells recognizing hepatocellular antigens are driven into a state of immune dysfunction, to identify a subset of KCs (referred to as KC2) that cross-presents hepatocellular antigens upon interleukin-2 (IL-2) administration, thus improving the antiviral function of T cells. Removing MHC-I from all KCs, including KC2, or selectively depleting KC2 impaired the capacity of IL-2 to revert the T cell dysfunction induced by intrahepatic priming. In summary, by sensing IL-2 and cross-presenting hepatocellular antigens, KC2 overcome the tolerogenic potential of the hepatic microenvironment, suggesting new strategies for boosting hepatic T cell immunity., Graphical abstract, Highlights • KCs are required for in vivo reinvigoration of intrahepatically primed T cells by IL-2 • KCs respond to IL-2 and cross-present hepatocellular Ags • Single-cell RNA-seq identifies two distinct populations of KCs • KC2s have enriched IL-2 sensing machinery and Ag presentation capacity, De Simone et al. delineate the mechanisms by which hepatocellularly primed HBV-specific CD8+ T cells acquire antiviral effector functions following IL-2 administration. These mechanisms rely on KCs and, in particular, on a hitherto unidentified KC subset, referred to as KC2, that is poised to respond to IL-2 and cross-present viral antigens.

Published
2021

21. 'Cloaking' on Time: A Cover-Up Act by Resident Tissue Macrophages

Author

Florent Ginhoux, Lai Guan Ng, and Camille Blériot

Subjects
0303 health sciences, Neutrophils, Variable size, Macrophages, Cell, Biology, General Biochemistry, Genetics and Molecular Biology, Article, Cell biology, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, Tissue damage, medicine, Macrophage, Neutrophil recruitment, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

Neutrophils are attracted to and generate dense swarms at sites of cell damage in diverse tissues, often extending the local disruption of organ architecture produced by the initial insult. Whether the inflammatory damage resulting from such neutrophil accumulation is an inescapable consequence of parenchymal cell death has not been explored. Using a combination of dynamic intravital imaging and confocal multiplex microscopy, we report here that tissue-resident macrophages rapidly sense the death of individual cells and extend membrane processes that sequester the damage, a process that prevents the initiation of the feedforward chemoattractant signaling cascade that results in neutrophil swarms. Through this “cloaking” mechanism, the resident macrophages prevent neutrophil-mediated inflammatory damage, maintaining tissue homeostasis in the face of local cell injury that occurs on a regular basis in many organs due to mechanical and other stresses.

Published
2019

22. Lipid-Associated Macrophages Control Metabolic Homeostasis in a Trem2-Dependent Manner

Author

Assaf Weiner, Zhaoyuan Liu, Aleksandra Deczkowska, Hagit Shapiro, Nir Lubezky, Patrick Lundgren, Baoguo Li, Ido Amit, Diego Jaitin, Hadas Keren-Shaul, Lorenz Adlung, Eyal David, Eran Elinav, Mitchell A. Lazar, Marco Colonna, Shai Meron Eldar, Hélène Descamps, Camille Blériot, Oren Shibolet, David A. Hill, Christoph A. Thaiss, Niv Zmora, and Florent Ginhoux

Subjects
Systems biology, Adipose Tissue, White, Cell, Adipose tissue, White adipose tissue, Biology, Intra-Abdominal Fat, Diet, High-Fat, General Biochemistry, Genetics and Molecular Biology, Monocytes, Article, Pathogenesis, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Glucose Intolerance, medicine, Macrophage, Animals, Humans, Obesity, Receptors, Immunologic, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Membrane Glycoproteins, Macrophages, Lipid Metabolism, Lipids, Cell biology, Mice, Inbred C57BL, medicine.anatomical_structure, Adipocyte hypertrophy, Single-Cell Analysis, 030217 neurology & neurosurgery, Signal Transduction
Abstract

Immune cells residing in white adipose tissue have been highlighted as important factors contributing to the pathogenesis of metabolic diseases, but the molecular regulators that drive adipose tissue immune cell remodeling during obesity remain largely unknown. Using index and transcriptional single-cell sorting, we comprehensively map all adipose tissue immune populations in both mice and humans during obesity. We describe a novel and conserved Trem2(+) lipid-associated macrophage (LAM) subset and identify markers, spatial localization, origin, and functional pathways associated with these cells. Genetic ablation of Trem2 in mice globally inhibits the downstream molecular LAM program, leading to adipocyte hypertrophy as well as systemic hypercholesterolemia, body fat accumulation, and glucose intolerance. These findings identify Trem2 signaling as a major pathway by which macrophages respond to loss of tissue-level lipid homeostasis, highlighting Trem2 as a key sensor of metabolic pathologies across multiple tissues and a potential therapeutic target in metabolic diseases.

Published
2019

23. Fate Mapping via Ms4a3-Expression History Traces Monocyte-Derived Cells

Author

Florent Ginhoux, Jinmiao Chen, Amanda Shin, Charles-Antoine Dutertre, Andreas Schlitzer, Zhaoyuan Liu, Lai Guan Ng, Camille Blériot, Bing Su, Immanuel Kwok, Svetoslav Chakarov, Honglin Wang, Weijie Huang, Xin Chen, Yaqi Gu, Zhiduo Liu, and Regine J. Dress

Subjects
Gene Expression, Inflammation, Cell Cycle Proteins, Biology, General Biochemistry, Genetics and Molecular Biology, Monocytes, 03 medical and health sciences, Mice, 0302 clinical medicine, Fate mapping, Granulocyte-Macrophage Progenitor Cells, medicine, Macrophage, Animals, Homeostasis, Progenitor cell, 030304 developmental biology, 0303 health sciences, Monocyte, Macrophages, Membrane Proteins, Dendritic cell, Embryonic stem cell, Cell biology, Hematopoiesis, medicine.anatomical_structure, MS4A3, Bone marrow, medicine.symptom, 030217 neurology & neurosurgery, Function (biology), Granulocytes
Abstract

SUMMARYMost tissue-resident macrophage (RTM) populations are seeded by waves of embryonic hematopoiesis and are self-maintained independently of a bone-marrow contribution during adulthood. A proportion of RTMs, however, is constantly replaced by blood monocytes and their functions compared to embryonic RTM remains unclear. The kinetics and extent of the contribution of circulating monocytes to RTM replacement during homeostasis, inflammation and disease is highly debated. Here, we identified Ms4a3 as a specific marker expressed by granulocyte-monocyte progenitors (GMPs) and subsequently generated Ms4a3TdT reporter and Ms4a3Cre-RosaTdT fate mapper models to follow monocytes and their progenies. Our Ms4a3Cre-RosaTdT model traced efficiently blood monocytes (97%) and granulocytes (100%), but no lymphocytes or tissue dendritic cells. Using this model, we precisely quantified the contribution of monocytes to the RTM pool during homeostasis and inflammation. The unambiguous identification of monocyte-derived cells will permit future studies of their function under any condition.

Published
2019

24. 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

25. Dying for a Cause: Regulated Necrosis of Tissue-Resident Macrophages upon Infection

Author

Marc Lecuit, Camille Blériot, Florent Ginhoux, Agency for science, technology and research [Singapore] (A*STAR), 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), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris]-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] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
0301 basic medicine, MESH: Listeria monocytogenes/physiology, MESH: Listeriosis/therapy, [SDV]Life Sciences [q-bio], Immunology, Innate immunology, MESH: Cell Self Renewal, Apoptosis, Regulated necrosis, Tissue protection, Mice, 03 medical and health sciences, MESH: Infection Control, MESH: Macrophages/physiology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Animals, Humans, Immunology and Allergy, Medicine, Listeriosis, MESH: Animals, Cell Self Renewal, MESH: Mice, Infection Control, MESH: Humans, business.industry, Macrophages, MESH: Apoptosis, Listeria monocytogenes, humanities, 3. Good health, 030104 developmental biology, [SDV.IMM]Life Sciences [q-bio]/Immunology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; We celebrated in 2016 the centenary of the death of Ilya Ilitch Metchnikov (1845–1916), the founding father of innate immunology. His studies on the description of macrophages, their phagocytic function, and their key role in eliminating microbes were recognized by the Nobel Prize in Physiology and Medicine, and constitute a cornerstone of immunology (https://www.nobelprize.org/nobel_prizes/medicine/laureates/1908/mechnikov-facts.html). Since then, macrophages are typically considered as tissue scavengers, that capture and destroy microbial intruders, thereby ensuring tissue protection and host defense against infections.

Published
2017

26. RIPK1, a key survival factor for hepatocytes

Author

Camille Blériot, Marc Lecuit, Biologie des Infections - Biology of Infection, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Immunology Network (SIgN), Biomedical Sciences Institute (BMSI), Agency for science, technology and research [Singapore] (A*STAR), 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), 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), 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 by Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Agence Nationale de la Recherche, LabEx IBEID, the Proantilis EU program and the European Research Council., Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP]-Institut des Maladies Génétiques Imagine [Paris], Centre collaborateur de l'OMS Listeria - Biologie des Infections (CCOMS), Institut des Maladies Génétiques Imagine [Paris], 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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
0301 basic medicine, Kupffer Cells, [SDV]Life Sciences [q-bio], education, Apoptosis, MESH: Receptor-Interacting Protein Serine-Threonine Kinases, Biology, Hepatitis, MESH: Hepatitis, MESH: Hepatocytes, Mice, 03 medical and health sciences, RIPK1, Animals, MESH: Animals, MESH: Mice, Hepatology, MESH: Apoptosis, 3. Good health, Cell biology, 030104 developmental biology, Receptor-Interacting Protein Serine-Threonine Kinases, Hepatocytes, Key (cryptography), [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Kupffer Cells, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Comment on : RIPK1 protects hepatocytes from Kupffer cells-mediated TNF-induced apoptosis in mouse models of PAMP-induced hepatitis. [J Hepatol. 2017]; International audience

Published
2017

27. Macrophage depletion in cancer therapy: A double-edged sword

Author

Florent Ginhoux and Camille Blériot

Subjects
0301 basic medicine, Macrophages, Immunology, Cancer therapy, Biology, Carcinoma, Lewis Lung, Mice, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Bone Marrow, Cancer research, Animals, Homeostasis, Erythropoiesis, Macrophage depletion, SWORD, 030215 immunology
Published
2018

28. RcnB Is a Periplasmic Protein Essential for Maintaining Intracellular Ni and Co Concentrations in Escherichia coli

Author

Florence Lagarde, Marie-Andrée Mandrand-Berthelot, Agnès Rodrigue, Géraldine Effantin, Camille Blériot, Microbiologie, adaptation et pathogénie (MAP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Trafic et signalisation membranaires chez les bactéries (MTSB), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), SIMS - Surfaces-(bio)Interfaces - Micro & Nano Systèmes (2011-2014), Institut des Sciences Analytiques (ISA), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), CNRS, IFCPAR grant no. 3709, INSA Lyon BQR, and the French Ministry of Research

Subjects
HOMEOSTASIS, EFFLUX, Physiology and Metabolism, Mutant, ATP-binding cassette transporter, Biology, medicine.disease_cause, Microbiology, 03 medical and health sciences, Copper Transport Proteins, Nickel, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, BINDING, Escherichia coli, medicine, COBALT, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Cation Transport Proteins, Molecular Biology, 030304 developmental biology, Metal ion homeostasis, 0303 health sciences, METAL RESISTANCE, 030306 microbiology, Escherichia coli Proteins, ABC TRANSPORTER, Biological Transport, Periplasmic space, ANAEROBIC GROWTH, Major facilitator superfamily, Transport protein, NICKEL TRANSPORTER NIKA, MUTANTS, Biochemistry, Biophysics, Efflux, Periplasmic Proteins, SYSTEM
Abstract

Nickel and cobalt are both essential trace elements that are toxic when present in excess. The main resistance mechanism that bacteria use to overcome this toxicity is the efflux of these cations out of the cytoplasm. RND (resistance-nodulation-cell division)- and MFS (major facilitator superfamily)-type efflux systems are known to export either nickel or cobalt. The RcnA efflux pump, which belongs to a unique family, is responsible for the detoxification of Ni and Co in Escherichia coli . In this work, the role of the gene yohN , which is located downstream of rcnA , is investigated. yohN is cotranscribed with rcnA , and its expression is induced by Ni and Co. Surprisingly, in contrast to the effect of deleting rcnA , deletion of yohN conferred enhanced resistance to Ni and Co in E. coli , accompanied by decreased metal accumulation. We show that YohN is localized to the periplasm and does not bind Ni or Co ions directly. Physiological and genetic experiments demonstrate that YohN is not involved in Ni import. YohN is conserved among proteobacteria and belongs to a new family of proteins; consequently, yohN has been renamed rcnB. We show that the enhanced resistance of rcnB mutants to Ni and Co and their decreased Ni and Co intracellular accumulation are linked to the greater efflux of these ions in the absence of rcnB . Taken together, these results suggest that RcnB is required to maintain metal ion homeostasis, in conjunction with the efflux pump RcnA, presumably by modulating RcnA-mediated export of Ni and Co to avoid excess efflux of Ni and Co ions via an unknown novel mechanism.

Published
2011

29. 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

30. Cu binding by the Escherichia coli metal-efflux accessory protein RcnB

Author

Agnès Rodrigue, David Pignol, Manon Gault, Pascal Arnoux, Camille Blériot, Marie-Andrée Mandrand-Berthelot, Erwan Gueguen, Microbiologie, adaptation et pathogénie (MAP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'ingénierie des systèmes macromoléculaires (LISM), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Microbiologie Environnementale et Moléculaire (MEM), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Biologie végétale et microbiologie environnementale - UMR7265 (BVME), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Mutant, Biophysics, medicine.disease_cause, Biochemistry, Divalent, Biomaterials, 03 medical and health sciences, Copper Transport Proteins, Nickel, Mutant protein, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Escherichia coli, medicine, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cation Transport Proteins, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, chemistry.chemical_classification, Metal ion homeostasis, 0303 health sciences, 030306 microbiology, Chemistry, Escherichia coli Proteins, Metals and Alloys, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cobalt, Periplasmic space, Ligand (biochemistry), [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Chemistry (miscellaneous), Efflux, Copper
Abstract

Divalent cations play fundamental roles in biological systems where they act as structural and reactive determinants. Their high reactivity with biomolecules has forced living cells to evolve specific pathways for their in vivo handling. For instance the excess of metal can be expelled by dedicated efflux systems. The E. coli RcnA efflux pump expels both Ni and Co. This pump functions together with the periplasmic protein RcnB to maintain metal ion homeostasis. To gain insights into the efflux mechanism, metal binding properties of RcnB were investigated. Initial screening of metal ions by fluorescence quenching revealed Cu as a potential ligand for RcnB. Non-denaturing mass spectrometry and ITC experiments revealed the binding of one Cu ion per monomer with a micromolar affinity. This set of in vitro techniques was broadened by in vivo experiments that showed the accuracy of Cu binding by RcnB. RcnB implication in Cu detoxification was questioned and growth experiments as well as transcriptional analysis excluded a role for RcnB in Cu adaptation. Finally a mutant in a conserved methionine residue (Met86) displayed altered Cu binding. This mutant protein when tested for its Ni and Co resistance capacity was unable to complement an rcn mutant. Taken together these data show that RcnB is a new Cu-binding protein that is strikingly involved in a Ni/Co efflux system.

Published
2014

31. The Escherichia coli metallo-regulator RcnR represses rcnA and rcnR transcription through binding on a shared operator site: Insights into regulatory specificity towards nickel and cobalt

Author

Corinne Dorel, Camille Blériot, Marie-Andrée Mandrand-Berthelot, Agnès Rodrigue, Safia Arous, Didier Blaha, Microbiologie, adaptation et pathogénie ( MAP ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Centre National de la Recherche Scientifique ( CNRS ), Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS ), Microbiologie, adaptation et pathogénie (MAP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Ecole Nationale Vétérinaire de Lyon (ENVL)

Subjects
Operator Regions, Genetic, Transcription, Genetic, Molecular Sequence Data, Repressor, Biology, medicine.disease_cause, Convergent promoters, Biochemistry, Primer extension, 03 medical and health sciences, chemistry.chemical_compound, Transcription (biology), Nickel, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Escherichia coli, Homeostasis, Amino Acid Sequence, Promoter Regions, Genetic, Gene, 030304 developmental biology, 0303 health sciences, [ SDV ] Life Sciences [q-bio], Base Sequence, 030306 microbiology, Escherichia coli Proteins, Membrane Proteins, Promoter, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, General Medicine, Cobalt, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Repressor Proteins, chemistry, Efflux, DNA, Protein Binding
Abstract

International audience; RcnA is an efflux pump responsible for Ni and Co detoxification in Escherichia coli. The expression of rcnA is induced by Ni and Co via the metallo-regulator RcnR. In the present work, the functioning of the promoter-operator region of rcnR and rcnA was investigated using primer extension and DNAse I footprinting experiments. We show that the promoters of rcnR and rcnA are convergent and that apo-RcnR binds on symmetrically located sequences in this intergenic region. Moreover, RcnR DNA binding is specifically modulated by one Ni or Co equivalent and not by other metals. In addition to rcnA, RcnR controls expression of its own gene in response to Ni and Co, but the two genes are differentially expressed.

Published
2010

32. Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming

Author

Patrick T F Kennedy, Valentina Bianchessi, Antonio Bertoletti, Mirela Kuka, Luca G. Guidotti, Giorgia De Simone, Giulia Barbiera, Francesco Andreata, Florent Ginhoux, Elisa Bono, Alessio Cantore, Leonardo Giustini, Eleonora Lusito, Weldy V. Bonilla, Alexandre P. Benechet, Matteo Iannacone, Paola Zordan, Kamini Kunasegaran, Daniel D. Pinschewer, Pietro Di Lucia, Camille Blériot, Renato Ostuni, Luigi Naldini, Francesco Cilenti, Nina Le Bert, Gloria González-Aseguinolaza, Valeria Fumagalli, Federica Moalli, Bénéchet, Alexandre P, De Simone, Giorgia, Di Lucia, Pietro, Cilenti, Francesco, Barbiera, Giulia, Le Bert, Nina, Fumagalli, Valeria, Lusito, Eleonora, Moalli, Federica, Bianchessi, Valentina, Andreata, Francesco, Zordan, Paola, Bono, Elisa, Giustini, Leonardo, Bonilla, Weldy V, Bleriot, Camille, Kunasegaran, Kamini, Gonzalez-Aseguinolaza, Gloria, Pinschewer, Daniel D, Kennedy, Patrick T F, Naldini, Luigi, Kuka, Mirela, Ginhoux, Florent, Cantore, Alessio, Bertoletti, Antonio, Ostuni, Renato, Guidotti, Luca G, Iannacone, Matteo, Benechet, A, De Simone, G, Di Lucia, P, Cilenti, F, Barbiera, G, Le Bert, N, Fumagalli, V, Lusito, E, Moalli, F, Bianchessi, V, Andreata, F, Zordan, P, Bono, E, Giustini, L, Bonilla, W, Bleriot, C, Kunasegaran, K, Gonzalez-Aseguinolaza, G, Pinschewer, D, Kennedy, P, Naldini, L, Kuka, M, Ginhoux, F, Cantore, A, Bertoletti, A, Ostuni, R, Guidotti, L, and Iannacone, M

Subjects
Male, 0301 basic medicine, Hepatitis B virus, Kupffer Cells, Cellular differentiation, Priming (immunology), CD8-Positive T-Lymphocytes, Biology, Lymphocyte Activation, Article, B7-H1 Antigen, Immune tolerance, Transcriptome, Intravital microscopy, Mice, 03 medical and health sciences, Cross-Priming, 0302 clinical medicine, HBV, Immune Tolerance, Animals, Humans, Cytotoxic T cell, Multidisciplinary, Effector, Cell Differentiation, Hepatitis B, Chromatin, 3. Good health, Cell biology, 030104 developmental biology, 030220 oncology & carcinogenesis, Hepatocytes, Interleukin-2, Female, CD8+ T cell, CD8
Abstract

The responses of CD8(+) T cells to hepatotropic viruses such as hepatitis B range from dysfunction to differentiation into effector cells, but the mechanisms that underlie these distinct outcomes remain poorly understood. Here we show that priming by Kupffer cells, which are not natural targets of hepatitis B, leads to differentiation of CD8(+) T cells into effector cells that form dense, extravascular clusters of immotile cells scattered throughout the liver. By contrast, priming by hepatocytes, which are natural targets of hepatitis B, leads to local activation and proliferation of CD8(+) T cells but not to differentiation into effector cells; these cells form loose, intravascular clusters of motile cells that coalesce around portal tracts. Transcriptomic and chromatin accessibility analyses reveal unique features of these dysfunctional CD8(+) T cells, with limited overlap with those of exhausted or tolerant T cells; accordingly, CD8(+) T cells primed by hepatocytes cannot be rescued by treatment with anti-PD-L1, but instead respond to IL-2. These findings suggest immunotherapeutic strategies against chronic hepatitis B infection.

Full Text
View/download PDF

33. 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

Catalog

Books, media, physical & digital resources
See catalog results