Search

Your search keyword '"Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany"' showing total 11 results
Start Over Author "Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany" Topic 0302 clinical medicine
11 results on '"Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany"'

1. Serum levels of hsa‐miR‐16‐5p , hsa‐miR‐29a‐3p , hsa‐miR‐150‐5p , hsa‐miR‐155‐5p and hsa‐miR ‐ 223‐3p and subsequent risk of chronic lymphocytic leukemia in the EPIC study

Author

Heiner Boeing, María Arestin, Aurelio Barricarte, Delphine Casabonne, Elio Riboli, Roel Vermeulen, Carlo La Vecchia, Alexandra Nieters, Federico Canzian, Julie A. Schmidt, Matthias B. Schulze, María Armesto, Rosario Tumino, Yolanda Benavente, Rudolf Kaaks, Salvatore Panico, María José Sánchez, Anna Karakatsani, Pilar Amiano, Caroline Besson, Marc J. Gunter, Giovanna Masala, Carlotta Sacerdote, María Dolores Chirlaque, Silvia de Sanjosé, Valeria Pala, Anne Tjønneland, Charles H. Lawrie, Antonia Trichopoulou, Elisabete Weiderpass, Eric J. Duell, Fatemeh Saberi Hosnijeh, Anja Olsen, Vittorio Perduca, Julia Seifert, Francesca Mancini, Laura Costas, CIBER de Epidemiología y Salud Pública (CIBERESP), Catalan Institute of Oncology (ICO-IDIBELL), Facultat de Medicina [Barcelona], Centre Hospitalier de Versailles André Mignot (CHV), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Épidémiologie des radiations, épidémiologie clinique des cancers et survie (U1018 (Équipe 3) ), Institut Gustave Roussy (IGR)-Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Department of Community Medicine, Faculty of Health Sciences, The Arctic University of Norway (UiT), Cancer Risk Factors and LifeStyle Epidemiology Unit, Cancer Research and Prevention Institute (ISPO), Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Department of Cancer Epidemiology, Mathématiques Appliquées Paris 5 (MAP5 - UMR 8145), Université Paris Descartes - Paris 5 (UPD5)-Institut National des Sciences Mathématiques et de leurs Interactions (INSMI)-Centre National de la Recherche Scientifique (CNRS), Mode de vie, génétique et santé : études intégratives et transgénérationnelles (U1018 (Équipe 9)), Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Tumori - National Cancer Institute [Milan], WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health, Dept of Hygiene, Epidemiology and Medical Statistics, University of Athens Medical School [Athens]-University of Athens Medical School [Athens], Hellenic Health Foundation, Department of Clinical Sciences and Community Health [Milan, Italy], Università degli Studi di Milano [Milano] (UNIMI), Civile - M.P.Arezzo Hospital, Nutrition and Metabolism Section, International Agency for Research on Cancer, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, CPO Piemonte, Department of Epidemiology, German Institute of Human Nutrition (DIfE), German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), School of Public Health [London, UK] (Faculty of Medicine), Imperial College London, Danish Cancer Society Research Center, Danish Cancer Society, Division of Environmental Epidemiology, Utrecht University [Utrecht]-Institute of Risk Assessment Sciences, Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, IRAS OH Epidemiology Chemical Agents, dIRAS RA-2, and Immunology

Subjects
Oncology, Male, DOWN-REGULATION, Cancer Research, PROGNOSIS, Chronic lymphocytic leukemia, ACTIVATION, 0302 clinical medicine, mir-223, Odds Ratio, Prospective Studies, Prospective cohort study, ComputingMilieux_MISCELLANEOUS, Area under the curve, Middle Aged, MIR-155, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Up-Regulation, Europe, DIFFERENTIATION, INFECTIONS, 030220 oncology & carcinogenesis, embryonic structures, Monoclonal B-cell lymphocytosis, Female, B-CELL LYMPHOCYTOSIS, Life Sciences & Biomedicine, prospective study, EXPRESSION, medicine.medical_specialty, MICRORNA SIGNATURE, miR-155, 03 medical and health sciences, Predictive Value of Tests, Internal medicine, medicine, Biomarkers, Tumor, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, Liquid biopsy, Science & Technology, business.industry, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, body regions, circulating miRNA, MicroRNAs, Case-Control Studies, chronic lymphocytic leukemia, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, serum, CLL
Abstract

Chronic lymphocytic leukemia (CLL) is an incurable disease accounting for almost one-third of leukemias in the Western world. Aberrant expression of microRNAs (miRNAs) is a well-established characteristic of CLL, and the robust nature of miRNAs makes them eminently suitable liquid biopsy biomarkers. Using a nested case–control study within the European Prospective Investigation into Cancer and Nutrition (EPIC), the predictive values of five promising human miRNAs (hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p), identified in a pilot study, were examined in serum of 224 CLL cases (diagnosed 3 months to 18 years after enrollment) and 224 matched controls using Taqman based assays. Conditional logistic regressions were applied to adjust for potential confounders. The median time from blood collection to CLL diagnosis was 10 years (p25–p75: 7–13 years). Overall, the upregulation of hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p was associated with subsequent risk of CLL [OR1∆Ct-unit increase (95%CI) = 1.42 (1.18–1.72), 1.64 (1.31–2.04) and 1.75 (1.31–2.34) for hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-29a-3p, respectively] and the strongest associations were observed within 10 years of diagnosis. However, the predictive performance of these miRNAs was modest (area under the curve

Published
2020
Full Text
View/download PDF

2. Carbohydrate-dependent B cell activation by fucose-binding bacterial lectins

Author

Marco Frensch, Michael Reth, Anne Imberty, Peter Fritz Müller, Rudolf Übelhart, Johanna Jakob, Ella Levit-Zerdoun, Alessia Landi, Isabel Wilhelm, Elias Hobeika, Roland Thuenauer, Winfried Römer, Hermann Eibel, Hassan Jumaa, Sarah Villringer, Julie Claudinon, Molecular immunology, Centre de Recherches sur les Macromolécules Végétales (CERMAV ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Compartimentation et dynamique cellulaires (CDC), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), and Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany

Subjects
Burkholderia, [SDV]Life Sciences [q-bio], Antigens, CD19, Carbohydrates, Syk, Fucose binding, Lymphocyte Activation, Biochemistry, Fucose, CD19, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Antigen, Bacterial Proteins, Lectins, Animals, Syk Kinase, Molecular Biology, 030304 developmental biology, CD86, Mice, Knockout, 0303 health sciences, B-Lymphocytes, biology, Cell Biology, Molecular biology, chemistry, Pseudomonas aeruginosa, biology.protein, Cytokine secretion, B7-2 Antigen, Intracellular, 030215 immunology, Signal Transduction
Abstract

International audience; Bacterial lectins are typically multivalent and bind noncovalently to specific carbohydrates on host tissues to facilitate bacterial adhesion. Here, we analyzed the effects of two fucose-binding lectins, BambL from Burkholderia ambifaria and LecB from Pseudomonas aeruginosa, on specific signaling pathways in B cells. We found that these bacterial lectins induced B cell activation, which, in vitro, was dependent on the cell surface expression of the B cell antigen receptor (BCR) and its coreceptor CD19, as well as on spleen tyrosine kinase (Syk) activity. The resulting release of intracellular Ca 2+ was followed by an increase in the cell surface abundance of the activation marker CD8, increased cytokine secretion, and subsequent cell death, replicating all of the events that are observed in vitro upon canonical and antigen-mediated B cell activation. Moreover, injection of BambL in mice resulted in a substantial, BCR-independent loss of B cells in the bone marrow with simultaneous, transient enlargement of the spleen (splenomegaly), as well as an increase in the numbers of splenic B cells and myeloid cells. Together, these data suggest that bacterial lectins can initiate polyclonal activation of B cells through their sole capacity to bind to fucose.

Published
2019
Full Text
View/download PDF

3. Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis

Author

Kari G. Chaffee, Sonja I. Berndt, Alexandra Nieters, Lindsay M. Morton, Stephen J. Chanock, Neil E. Caporaso, Delphine Casabonne, Karin E. Smedby, Aaron D. Norman, Celine M. Vachon, James McKay, Pierluigi Cocco, Christine F. Skibola, Timothy G. Call, Nicola J. Camp, Martha Glenn, Jacqueline Clavel, Mark Liebow, Paolo Boffetta, James B. Johnston, John J. Spinelli, James R. Cerhan, Lynn R. Goldin, Hans-Olov Adami, Nathaniel Rothman, Yolanda Benavente, J. Brice Weinberg, Paul Brennan, Paige M. Bracci, Marc Maynadié, Dennis P. Robinson, Geffen Kleinstern, Silvia de Sanjosé, Susan L. Slager, Tait D. Shanafelt, Lucia Conde, Bengt Glimelius, Richard K. Severson, Jose F. Leis, Wendy Cozen, Claire M. Vajdic, Angela Brooks-Wilson, Mads Melbye, Henrik Hjalgrim, Karen Curtin, Neil E. Kay, Curtis A. Hanson, Alain Monnereau, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Catalan Institute of Oncology, Department of Epidemiology, Catalan Institute of Oncology (ICO), Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], Uppsala Universitet [Uppsala], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Registre des hémopathies malignes de Côte d'Or, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Bourgogne Franche-Comté [COMUE] (UBFC), International Agency for Cancer Research (IACR), Mayo Clinic [Rochester], Laboratoire Interdisciplinaire de Spectroscopie Electronique (LISE), Facultés Universitaires Notre Dame de la Paix (FUNDP), Registre des hémopathies malignes de la Gironde, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Cancer environnement (EPICENE ), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe 7 : EPICEA - Epidémiologie des cancers de l'enfant et de l'adolescent (CRESS - U1153), Université Paris Descartes - Paris 5 (UPD5)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Huntsman Cancer Institute, Norris Comprehensive Cancer Center, Wayne State University [Detroit], Division of Cancer Epidemiology and Genetics, National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), Emory University [Atlanta, GA], Cancer Center Karolinska [Karolinska Institutet] (CCK), Department of Psychiatry, Facultés Universitaires Notre Dame de la Paix (FUNDP) - Namur, Institut Bergonié - CRLCC Bordeaux, Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Kleinstern, Geffen, Camp, Nicola J., Goldin, Lynn R., Vachon, Celine M., Vajdic, Claire M., De Sanjose, Silvia, Weinberg, J. Brice, Benavente, Yolanda, Casabonne, Delphine, Liebow, Mark, Nieters, Alexandra, Hjalgrim, Henrik, Melbye, Mad, Glimelius, Bengt, Adami, Hans-Olov, Boffetta, Paolo, Brennan, Paul, Maynadie, Marc, McKay, Jame, Cocco, Pier Luigi, Shanafelt, Tait D., Call, Timothy G., Norman, Aaron D., Hanson, Curti, Robinson, Denni, Chaffee, Kari G., Brooks-Wilson, Angela R., Monnereau, Alain, Clavel, Jacqueline, Glenn, Martha, Curtin, Karen, Conde, Lucia, Bracci, Paige M., Morton, Lindsay M., Cozen, Wendy, Severson, Richard K., Chanock, Stephen J., Spinelli, John J., Johnston, James B., Rothman, Nathaniel, Skibola, Christine F., Leis, Jose F., Kay, Neil E., Smedby, Karin E., Berndt, Sonja I., Cerhan, James R., Caporaso, Neil, and Slager, Susan L.

Subjects
Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Lymphocytosis, Clinical Trials and Observations, Chronic lymphocytic leukemia, Immunology, Single-nucleotide polymorphism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Polymorphism, Single Nucleotide, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, immune system diseases, Internal medicine, hemic and lymphatic diseases, Genotype, Odds Ratio, medicine, Humans, Genetic Predisposition to Disease, 10. No inequality, Aged, Aged, 80 and over, B-Lymphocytes, business.industry, Confounding, Cell Biology, Hematology, Odds ratio, Middle Aged, medicine.disease, Leukemia, Lymphocytic, Chronic, B-Cell, 3. Good health, 030104 developmental biology, Genetic epidemiology, Genetic Loci, 030220 oncology & carcinogenesis, Monoclonal B-cell lymphocytosis, Female, medicine.symptom, business
Abstract

IF 15.132 (2017); International audience; Inherited loci have been found to be associated with risk of chronic lymphocytic leukemia (CLL). A combined polygenic risk score (PRS) of representative single nucleotide polymorphisms (SNPs) from these loci may improve risk prediction over individual SNPs. Herein, we evaluated the association of a PRS with CLL risk and its precursor, monoclonal B-cell lymphocytosis (MBL). We assessed its validity and discriminative ability in an independent sample and evaluated effect modification and confounding by family history (FH) of hematological cancers. For discovery, we pooled genotype data on 41 representative SNPs from 1499 CLL and 2459 controls from the InterLymph Consortium. For validation, we used data from 1267 controls from Mayo Clinic and 201 CLL, 95 MBL, and 144 controls with a FH of CLL from the Genetic Epidemiology of CLL Consortium. We used odds ratios (ORs) to estimate disease associations with PRS and c-statistics to assess discriminatory accuracy. In InterLymph, the continuous PRS was strongly associated with CLL risk (OR, 2.49; P = 4.4 × 10-94). We replicated these findings in the Genetic Epidemiology of CLL Consortium and Mayo controls (OR, 3.02; P = 7.8 × 10-30) and observed high discrimination (c-statistic = 0.78). When jointly modeled with FH, PRS retained its significance, along with FH status. Finally, we found a highly significant association of the continuous PRS with MBL risk (OR, 2.81; P = 9.8 × 10-16). In conclusion, our validated PRS was strongly associated with CLL risk, adding information beyond FH. The PRS provides a means of identifying those individuals at greater risk for CLL as well as those at increased risk of MBL, a condition that has potential clinical impact beyond CLL.

Published
2018
Full Text
View/download PDF

4. Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC)

Author

John J. Spinelli, Graham G. Giles, Parveen Bhatti, Alexandra Nieters, Dennis D. Weisenburger, Anneclaire J. De Roos, Lenka Foretova, Paolo Boffetta, Mark P. Purdue, Nikolaus Becker, Nicola J. Camp, Brian C.-H. Chiu, Marc Maynadié, Guido Tricot, Silvia de Sanjosé, Pier Luigi Cocco, Dalsu Baris, Yawei Zhang, Veronique Benhaim-Luzon, Kirsten B. Moysich, Laura Costas, Anthony Staines, Elizabeth E. Brown, Wendy Cozen, Paul Brennan, Brenda M. Birmann, Gabriella Andreotti, Brigham and Women's Hospital [Boston], National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), CIBER de Epidemiología y Salud Pública (CIBERESP), Facultat de Medicina [Barcelona], Catalan Institute of Oncology, Masaryk University [Brno] (MUNI), The Cancer Council Victoria, Université de Bourgogne (UB), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Registre des hémopathies malignes de Côte d'Or, Department of Cancer Prevention and Control, Roswell Park Cancer Institute [Buffalo], Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, University of Iowa [Iowa City], Department of Pathology (City of Hope, Duarte, California), City of Hope Comprehensive Cancer Center [Duarte], Yale School of Public Health (YSPH), Yale University School of Medicine, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Department of Health and Human Services, German Cancer Research Center [Heidelberg] ( DKFZ ), Helmholtz-Gemeinschaft, Masaryk University, Université de Bourgogne ( UB ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Department of Internal Medicine, University of Iowa, Iowa City, Iowa, Yale School of Public Health ( YSPH ), Yale School of Medicine, and Birmann, B.M. and Andreotti, G. and De Roos, A.J. and Camp, N.J. and Chiu, B.C.H. and Spinelli, J.J. and Becker, N. and Benhaim-Luzon, V. and Bhatti, P. and Boffetta, P. and Brennan, P. and Brown, E.E. and Cocco, P. and Costas, L. and Cozen, W. and De Sanjose, S. and Foretova, L. and Giles, G.G. and Maynadie, M. and Moysich, K. and Nieters, A. and Staines, A. and Tricot, G. and Weisenburger, D. and Zhang, Y. and Baris, D. and Purdue, M.P.

Subjects
0301 basic medicine, Male, obesity, procedure, Epidemiology, groups by age, Overweight, cancer risk, Body Mass Index, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, study design, Risk Factors, middle aged, Young adult, risk factor, Adult, Multiple myeloma, 2. Zero hunger, education.field_of_study, anthropometry, adult, risk assessment, 3. Good health, multiple myeloma, female, Oncology, priority journal, 030220 oncology & carcinogenesis, young adult, medicine.symptom, Case-Control Studie, medicine.medical_specialty, multivariate logistic regression analysi, Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, Internal medicine, medicine, Humans, human, education, Aged, business.industry, Case-control study, Anthropometry, case control study, medicine.disease, Confidence interval, 030104 developmental biology, Endocrinology, Case-Control Studies, pathology, business, Body mass index, body ma
Abstract

Background: Multiple myeloma risk increases with higher adult body mass index (BMI). Emerging evidence also supports an association of young adult BMI with multiple myeloma. We undertook a pooled analysis of eight case–control studies to further evaluate anthropometric multiple myeloma risk factors, including young adult BMI.Methods: We conducted multivariable logistic regression analysis of usual adult anthropometric measures of 2,318 multiple myeloma cases and 9,609 controls, and of young adult BMI (age 25 or 30 years) for 1,164 cases and 3,629 controls.Results: In the pooled sample, multiple myeloma risk was positively associated with usual adult BMI; risk increased 9% per 5-kg/m2 increase in BMI [OR, 1.09; 95% confidence interval (CI), 1.04–1.14; P = 0.007]. We observed significant heterogeneity by study design (P = 0.04), noting the BMI–multiple myeloma association only for population-based studies (Ptrend = 0.0003). Young adult BMI was also positively associated with multiple myeloma (per 5-kg/m2; OR, 1.2; 95% CI, 1.1–1.3; P = 0.0002). Furthermore, we observed strong evidence of interaction between younger and usual adult BMI (Pinteraction Conclusions: BMI-associated increases in multiple myeloma risk were highest for individuals who were overweight or obese throughout adulthood.Impact: These findings provide the strongest evidence to date that earlier and later adult BMI may increase multiple myeloma risk and suggest that healthy BMI maintenance throughout life may confer an added benefit of multiple myeloma prevention. Cancer Epidemiol Biomarkers Prev; 26(6); 876–85. ©2017 AACR.

Published
2017
Full Text
View/download PDF

5. Mycobacteria exploit nitric oxide-induced transformation of macrophages into permissive giant cells

Author

Florens Lohrmann, Magdeldin Elgizouli, Carsten J. Kirschning, Anne Kathrin Lösslein, Anna Lena Illert, Julia Senges, Manfred Fliegauf, Kourosh Gharun, Philipp Henneke, Maximilian Seidl, Martine Gilleron, Antigoni Triantafyllopoulou, Martina Vavra, Kristina Schachtrup, Marco Alber, Julia Kolter, Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées

Subjects
0301 basic medicine, medicine.drug_class, DNA damage, Cellular differentiation, [SDV]Life Sciences [q-bio], Medizin, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, Antimycobacterial, Nitric Oxide, Biochemistry, Giant Cells, Nitric oxide, Mycobacterium, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Genetics, medicine, Macrophage, Animals, Humans, Molecular Biology, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, 030306 microbiology, Effector, Macrophages, Cell Differentiation, Articles, biology.organism_classification, Genes, p53, Corrigenda, Cell biology, 030104 developmental biology, chemistry, Giant cell, Immunology, 030215 immunology, DNA Damage
Abstract

Immunity to mycobacteria involves the formation of granulomas, characterized by a unique macrophage (MΦ) species, so‐called multinucleated giant cells (MGC). It remains unresolved whether MGC are beneficial to the host, that is, by prevention of bacterial spread, or whether they promote mycobacterial persistence. Here, we show that the prototypical antimycobacterial molecule nitric oxide (NO), which is produced by MGC in excessive amounts, is a double‐edged sword. Next to its antibacterial capacity, NO propagates the transformation of MΦ into MGC, which are relatively permissive for mycobacterial persistence. The mechanism underlying MGC formation involves NO‐induced DNA damage and impairment of p53 function. Moreover, MGC have an unsurpassed potential to engulf mycobacteria‐infected apoptotic cells, which adds a further burden to their antimycobacterial capacity. Accordingly, mycobacteria take paradoxical advantage of antimicrobial cellular efforts by driving effector MΦ into a permissive MGC state.

Published
2017
Full Text
View/download PDF

6. Streptococci Engage TLR13 on Myeloid Cells in a Site-Specific Fashion

Author

Sachin D. Deshmukh, Reinhild Feuerstein, Zhijian J. Chen, Patrick Trieu-Cuot, Tobias Goldmann, Philipp Henneke, Kourosh Gharun, Claudia Waskow, Julia Kolter, Roland Elling, Carsten J. Kirschning, Evelyne Spoeri, Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), institute of neuropathology, University of Freiburg [Freiburg], Regeneration in Hematopoiesis and Animal Models of Hematopoiesis, Faculty of Medicine, Dresden University of Technology, Southwestern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Institute of Medical Microbiology, University of Duisbourg-Essen, Center for sepsis control care, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Colon, Immunology, Medizin, Mice, Transgenic, Biology, Hemolysis, Streptococcus agalactiae, Mice, 03 medical and health sciences, 0302 clinical medicine, Dermis, Immunity, Streptococcal Infections, medicine, Animals, Immunology and Allergy, Progenitor cell, Receptor, Immunity, Mucosal, Skin, Mice, Knockout, Lamina propria, Innate immune system, Microglia, Macrophages, Toll-Like Receptors, Membrane Transport Proteins, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Mice, Inbred C57BL, 030104 developmental biology, medicine.anatomical_structure, Mucosal immunology, Organ Specificity, Host-Pathogen Interactions, Cytokines, 030215 immunology
Abstract

Streptococci are common human colonizers with a species-specific mucocutaneous distribution. At the same time, they are among the most important and most virulent invasive bacterial pathogens. Thus, site-specific cellular innate immunity, which is predominantly executed by resident and invading myeloid cells, has to be adapted with respect to streptococcal sensing, handling, and response. In this article, we show that TLR13 is the critical mouse macrophage (MΦ) receptor in the response to group B Streptococcus, both in bone marrow–derived MΦs and in mature tissue MΦs, such as those residing in the lamina propria of the colon and the dermis, as well as in microglia. In contrast, TLR13 and its chaperone UNC-93B are dispensable for a potent cytokine response of blood monocytes to group B Streptococcus, although monocytes serve as the key progenitors of intestinal and dermal MΦs. Furthermore, a specific role for TLR13 with respect to MΦ function is supported by the response to staphylococci, where TLR13 and UNC-93B limit the cytokine response in bone marrow–derived MΦs and microglia, but not in dermal MΦs. In summary, TLR13 is a critical and site-specific receptor in the single MΦ response to β-hemolytic streptococci.

Published
2016
Full Text
View/download PDF

7. A Pooled Analysis of Reproductive Factors, Exogenous Hormone Use, and Risk of Multiple Myeloma among Women in the International Multiple Myeloma Consortium

Author

Anneclaire J. De Roos, Laura Costas, Djordje Atanackovic, Lenka Foretova, Jonathan N. Hofmann, Elisabeth E. Brown, Sophia S. Wang, Pierluigi Cocco, Alexandra Nieters, Dalsu Baris, Anthony Staines, Paul Brennan, Nicola J. Camp, Guido Tricot, Brenda M. Birmann, Nikolaus Becker, Marc Maynadié, Brice H. Lambert, Kirsten B. Moysich, Silvia de Sanjosé, Paolo Boffetta, Facultat de Medicina [Barcelona], CIBER de Epidemiología y Salud Pública (CIBERESP), Catalan Institute of Oncology (ICO-IDIBELL), Department of Epidemiology, University of Alabama at Birmingham, Harvard Medical School [Boston] ( HMS ), Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], Department of Cancer Prevention and Control, Roswell Park Cancer Institute [Buffalo], Department of Environmental and Occupational Health, Drexel University School of Public Health, Philadelphia, Pennsylvania, Division of Cancer Epidemiology and Genetics, National Institutes of Health ( NIH ) -National Cancer Institute ( NIH ), Division of Cancer Etiology, Department of Population Sciences, City of Hope and Beckman Research Institute, Duarte, California, Division of Hematology and Hematologic Malignancies, University of Utah School of Medicine and Huntsman Cancer Institute, Salt Lake City, Utah, Department of Internal Medicine, University of Iowa, Iowa City, Iowa, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer ( CIRC - IARC ), Organisation mondiale de la santé (OMS/WHO), Universita degli Studi di Cagliari [Cagliari], Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, Deutsches Krebsforschungszentrum, Centre de ressources biologiques Ferdinand Cabanne [Dijon] ( CRB Ferdinand Cabanne ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Centre d'épidémiologie des populations ( CEP ), Université de Bourgogne ( UB ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Masaryk Memorial Cancer Institute and Medical Faculty of Masaryk University, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai [New York], School of Public Health and Population Science, University College Dublin, Department of Pathology, University of Alabama at Birmingham, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, Alabama, Costas, L., Lambert, B.H., Birmann, B.M., Moysich, K.B., De Roos, A.J., Hofmann, J.N., Baris, D., Wang, S.S., Camp, N.J., Tricot, G., Atanackovic, D., Brennan, P., Cocco, P., Nieters, A., Becker, N., Maynadié, M., Foretová, L., Boffetta, P., Staines, A., Brown, E.E., De Sanjosé, S., University of Alabama at Birmingham [ Birmingham] (UAB), Harvard Medical School [Boston] (HMS), Drexel University, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), City of Hope National Medical Center, University of Iowa [Iowa City], Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Centre de ressources biologiques Ferdinand Cabanne [Dijon] (CRB Ferdinand Cabanne), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre d'épidémiologie des populations (CEP), Université de Bourgogne (UB)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Icahn School of Medicine at Mount Sinai [New York] (MSSM), and University College Dublin [Dublin] (UCD)

Subjects
Male, Epidemiology, medicine.medical_treatment, Physiology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, Risk Factors, Odds Ratio, Gonadal, 030212 general & internal medicine, Reproductive History, Multiple myeloma, Incidence, Middle Aged, Statistical, Prognosis, 3. Good health, Postmenopause, Contraception, Oncology, Transgender hormone therapy, 030220 oncology & carcinogenesis, Meta-analysis, Regression Analysis, Female, Multiple Myeloma, Factor Analysis, Adult, Hormone Replacement Therapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, 03 medical and health sciences, Young Adult, Meta-Analysis as Topic, Reproductive factors, exogenous hormone use, and risk of multiple myeloma, medicine, Confidence Intervals, Humans, Neoplasm Staging, Steroid Hormones, business.industry, Case-control study, Odds ratio, medicine.disease, Hormones, Logistic Models, Hormonal contraception, Case-Control Studies, Sample Size, Immunology, Hormone therapy, business, Hormone, Follow-Up Studies, Meta-Analysis
Abstract

Background: Female sex hormones are known to have immunomodulatory effects. Therefore, reproductive factors and exogenous hormone use could influence the risk of multiple myeloma in women. However, the role of hormonal factors in multiple myeloma etiology remains unclear because previous investigations were underpowered to detect modest associations. Methods: We conducted a pooled analysis of seven case–control studies included in the International Multiple Myeloma Consortium, with individual data on reproductive factors and exogenous hormone use from 1,072 female cases and 3,541 female controls. Study-specific odds ratios and corresponding 95% confidence intervals (CI) were estimated using logistic regression and pooled analyses were conducted using random effects meta-analyses. Results: Multiple myeloma was not associated with reproductive factors, including ever parous [OR = 0.92; 95% confidence interval (CI), 0.68–1.25], or with hormonal contraception use (OR = 1.04; 95% CI, 0.80–1.36). Postmenopausal hormone therapy users had nonsignificantly reduced risks of multiple myeloma compared with never users, but this association differed across centers (OR = 0.65; 95% CI, 0.37–1.15, I2 = 76.0%, Pheterogeneity = 0.01). Conclusions: These data do not support a role for reproductive factors or exogenous hormones in myelomagenesis. Impact: Incidence rates of multiple myeloma are higher in men than in women, and sex hormones could influence this pattern. Associations with reproductive factors and exogenous hormone use were inconclusive despite our large sample size, suggesting that female sex hormones may not play a significant role in multiple myeloma etiology. Cancer Epidemiol Biomarkers Prev; 25(1); 217–21. ©2015 AACR.

Published
2015
Full Text
View/download PDF

8. The Extended Clinical Phenotype Of 64 Patients With Dedicator Of Cytokinesis 8 Deficiency

Author

Tim Niehues, Karin R. Engelhardt, Mehmet Kilic, Raif S. Geha, Necil Kutukculer, Zeina Baz, Sevgi Keles, Cristina Glocker, Caner Aytekin, Ozden Sanal, Ismail Reisli, Zahra Pourpak, Ferah Genel, Mustafa Yilmaz, Alison Jones, B Gaspar, Elena C. Sigmund, Nermeen Galal, Yildiz Camcioglu, Michel J. Massaad, Amos Etzioni, Turkan Patiroglu, Laura E. Graham, Maria Cristina Pietrogrande, Majed Dasouki, Andrew R. Gennery, S Weinspach, G Dueckers, Michael E. Gertz, Monia Khemiri, M. R. Barbouche, Mehdi Yeganeh, Imen Ben-Mustapha, Shiva Saghafi, Bodo Grimbacher, Salem Al-Tamemi, Andrew J. Cant, A. Sassi, Gérard Lefranc, Ayse Metin, Vassilios Lougaris, Ayper Somer, Fethi Mellouli, Ekrem Unal, Alexandra F. Freeman, Jeannette Boutros, Ruben Ceja, Jens Thiel, André Mégarbané, Sara Sebnem Kilic, Talal A. Chatila, Mohamed Bejaoui, Alejandro A. Schäffer, Ilhan Tezcan, Waleed Al-Herz, Peter D. Arkwright, Ilka Schulze, Çocuk Sağlığı ve Hastalıkları, University College of London [London] (UCL), National Center for Biotechnology Information (NCBI), David Geffen School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California-University of California, Freiburg University Medical Center, Institute of Mechanical Systems, Department of Mechanical and Process Engineering, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Tehran University of Medical Sciences (TUMS), Laboratoire d'Immunopathologie, Vaccinologie et Génétique Moléculaire (LVGM), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratory for the Study of Skeletal Disorders and Rehabilitation (Boston, USA), Harvard Combined Orthopaedic Residency (USA), Department of Peadiatric Immuno-Haematology, National Bone Marrow Transplantation, Laboratoire d'immunologie clinique [Institut Pasteur de Tunis], Pediatrics Department A, Children's Hospital of Tunis, Tunis, Tunisia, National Institute of Allergy and Infectious Diseases [Bethesda] (NIAID-NIH), National Institutes of Health [Bethesda] (NIH), Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, Kuwait University, the Pediatric Immunology Unit, SB Ankara Diskapi Children’s Hospital, Ankara University School of Medicine [Turkey], Tehran University of Medical Sciences, School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU)-Tehran University of Medical Sciences, Helios Klinikum Krefeld - Helios Klinikum Krefeld, Center of Child and Adolescent Medicine, Heinrich-Heine-University Dusseldorf, Department of Pediatrics, Division of Pediatric Hematology and Oncology, Faculty of Medicine, Erciyes University, Kayseri, Turkey, Department of Pediatrics, Division of Pediatric Immunology, Faculty of Medicine, Erciyes University, Kayseri, Turkey, Department of Oncology, Aalborg Hospital, Aarhus University [Aarhus], Behcet Uz State Hospital Division of Pediatric Immunology, Izmir, Dis Training & Res Ctr, Department of Pediatrics, Ege University, Istanbul University, Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ), Necmettin Erbakan Univ, Cerrahpasa Medical School, Université d' Istanbul, Newcastle General Hospital, the Department of Maternal and Pediatric Sciences, University of Milan, Fondazione IRCCS Policlinico Milano, the Department of Pediatrics, St George Hospital University Medical Center, Beirut, Sultan Qaboos University (SQU), Université Montpellier 2 - Sciences et Techniques (UM2), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Primary Immunodeficiency Clinic, Cairo University Specialized Pediatric Hospital, Pediatrics Department, Bone Marrow Transplantation Center, Tunis, Tunisia., Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), and Çukurova Üniversitesi

Subjects
CD4-Positive T-Lymphocytes, Male, Allergy, Support Vector Machine, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Hypereosinophilia, Hematopoietic stem cell transplantation, CD8-Positive T-Lymphocytes, autosomal recessive hyper-IgE syndrome, dedicator of cytokinesis 8, hyper-IgE syndrome, Molluscum contagiosum, Primary combined immunodeficiency, signal transducer and activator of transcription 3, Adolescent, Adult, Antigens, Bacterial, Antigens, Viral, Bacterial Infections, Child, Child, Preschool, Eosinophils, Female, Guanine Nucleotide Exchange Factors, Humans, Immunoglobulin E, Immunoglobulin M, Infant, Job Syndrome, Lymphocyte Count, Middle Aged, Mutation, STAT3 Transcription Factor, Skin Diseases, Survival Analysis, Virus Diseases, Phenotype, Immunology and Allergy, Immunology, 0302 clinical medicine, MESH: Child, MESH: Guanine Nucleotide Exchange Factors, Viral, Immunodeficiency, 0303 health sciences, MESH: Middle Aged, Respiratory tract infections, Progressive multifocal leukoencephalopathy, MESH: Immunoglobulin E, MESH: Support Vector Machine, Bacterial, MESH: STAT3 Transcription Factor, MESH: CD4-Positive T-Lymphocytes, MESH: Infant, MESH: CD8-Positive T-Lymphocytes, MESH: Immunoglobulin M, 3. Good health, MESH: Virus Diseases, MESH: Survival Analysis, Dock8, medicine.symptom, MESH: Antigens, Viral, MESH: Lymphocyte Count, MESH: Mutation, MESH: Bacterial Infections, MESH: Skin Diseases, Biology, MESH: Phenotype, 03 medical and health sciences, MESH: Eosinophils, medicine, Antigens, Preschool, 030304 developmental biology, MESH: Adolescent, MESH: Humans, MESH: Job Syndrome, MESH: Child, Preschool, MESH: Adult, medicine.disease, MESH: Male, DOCK8 Deficiency, MESH: Female, MESH: Antigens, Bacterial, 030215 immunology
Abstract

PubMedID: 25724123 Background Mutations in dedicator of cytokinesis 8 (DOCK8) cause a combined immunodeficiency (CID) also classified as autosomal recessive (AR) hyper-IgE syndrome (HIES). Recognizing patients with CID/HIES is of clinical importance because of the difference in prognosis and management. Objectives We sought to define the clinical features that distinguish DOCK8 deficiency from other forms of HIES and CIDs, study the mutational spectrum of DOCK8 deficiency, and report on the frequency of specific clinical findings. Methods Eighty-two patients from 60 families with CID and the phenotype of AR-HIES with (64 patients) and without (18 patients) DOCK8 mutations were studied. Support vector machines were used to compare clinical data from 35 patients with DOCK8 deficiency with those from 10 patients with AR-HIES without a DOCK8 mutation and 64 patients with signal transducer and activator of transcription 3 (STAT3) mutations. Results DOCK8-deficient patients had median IgE levels of 5201 IU, high eosinophil levels of usually at least 800/µL (92% of patients), and low IgM levels (62%). About 20% of patients were lymphopenic, mainly because of low CD4+ and CD8+ T-cell counts. Fewer than half of the patients tested produced normal specific antibody responses to recall antigens. Bacterial (84%), viral (78%), and fungal (70%) infections were frequently observed. Skin abscesses (60%) and allergies (73%) were common clinical problems. In contrast to STAT3 deficiency, there were few pneumatoceles, bone fractures, and teething problems. Mortality was high (34%). A combination of 5 clinical features was helpful in distinguishing patients with DOCK8 mutations from those with STAT3 mutations. Conclusions DOCK8 deficiency is likely in patients with severe viral infections, allergies, and/or low IgM levels who have a diagnosis of HIES plus hypereosinophilia and upper respiratory tract infections in the absence of parenchymal lung abnormalities, retained primary teeth, and minimal trauma fractures. © 2015 American Academy of Allergy, Asthma & Immunology. National Institutes of Health: R01AI065617 National Institutes of Health: R21AI087627

Published
2015
Full Text
View/download PDF

9. High Levels of SOX5 Decrease Proliferative Capacity of Human B Cells, but Permit Plasmablast Differentiation

Author

Nadine Eliane Schmit, Cemil Korcan Ayata, Wolfgang Schuh, Kerstina Melkaoui, Zhibing Zhang, Beate Fischer, Luisa Moehle, Els Verhoeyen, Hermann Eibel, Sachin D. Deshmukh, Maximilian Seidl, Reinhard E. Voll, Marta Rizzi, Hans-Hartmut Peter, Mirzokhid Rakhmanov, Klaus Warnatz, Susanne Unger, Anne-Kathrin Kienzler, Heiko Sic, Ulrich Salzer, François-Loïc Cosset, Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, Freiburg University Medical Center, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Virginia Commonwealth University (VCU), Virus enveloppés, vecteurs et immunothérapie – Enveloped viruses, Vectors and Immuno-therapy (EVIR), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universitäts Klinikum Freiburg = University Medical Center Freiburg (Uniklinik), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and 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)

Subjects
B Cells, Cellular differentiation, Messenger, lcsh:Medicine, Lymphocyte Activation, Cell Fate Determination, Autoantigens, White Blood Cells, 0302 clinical medicine, Medizinische Fakultät, Animal Cells, Medicine and Health Sciences, lcsh:Science, Cells, Cultured, Regulation of gene expression, 0303 health sciences, Multidisciplinary, Tumor, Cultured, biology, Cell Differentiation, Cell biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cellular Types, SOXD Transcription Factors, Research Article, Cells, Immune Cells, Naive B cell, Immunology, Plasma Cells, Cell Line, 03 medical and health sciences, Cell Line, Tumor, medicine, Humans, ddc:610, RNA, Messenger, B cell, 030304 developmental biology, Cell Proliferation, CD40, Blood Cells, lcsh:R, Germinal center, Biology and Life Sciences, Cell Biology, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, B-1 cell, Gene Expression Regulation, Cell culture, biology.protein, RNA, lcsh:Q, Clinical Immunology, Developmental Biology
Abstract

International audience; Currently very little is known about the differential expression and function of the transcription factor SOX5 during B cell maturation. We identified two new splice variants of SOX5 in human B cells, encoding the known L-SOX5B isoform and a new shorter isoform L-SOX5F. The SOX5 transcripts are highly expressed during late stages of B-cell differentiation, including atypical memory B cells, activated CD21low B cells and germinal center B cells of tonsils. In tonsillar sections SOX5 expression was predominantly polarized to centrocytes within the light zone. After in vitro stimulation, SOX5 expression was down-regulated during proliferation while high expression levels were permissible for plasmablast differentiation. Overexpression of L-SOX5F in human primary B lymphocytes resulted in reduced proliferation, less survival of CD138neg B cells, but comparable numbers of CD138+CD38hi plasmablasts compared to control cells. Thus, our findings describe for the first time a functional role of SOX5 during late B cell development reducing the proliferative capacity and thus potentially affecting the differentiation of B cells during the germinal center response.

Published
2014
Full Text
View/download PDF

10. RNA and beta-Hemolysin of Group B Streptococcus Induce Interleukin-1 beta ( IL-1 beta) by Activating NLRP3 Inflammasomes in Mouse Macrophages

Author

Katherine A. Fitzgerald, Vijay A. K. Rathinam, Bornali Bhattacharjee, Parisa Kalantari, Egil Lien, Rosane B. DeOliveira, Anubhab Nandy, Jennie Chan, Shubhendu Ghosh, Douglas T. Golenbock, Philipp Henneke, Patrick Trieu-Cuot, Shrutie Sharma, Fabianno Ferreira, Arnaud Firon, Te-Chen Tzeng, Neal S. Silverman, Brian G. Monks, Rahul Gupta, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Laboratório de Inflamação e Imunidade, Universidade Federal do Rio de Janeiro (UFRJ), Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, This work was supported, in whole or in part, by National Institutes of Health Grant RO1 AI52455 (to D. T. G., P. H., and P. T.-C.) and U24 AI082663 (to D. T. G., N. S., E. L., and S. G.) and by the German Research Council (DFG HE 3127/5-1 to P. H.)., and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Inflammasomes, medicine.medical_treatment, Interleukin-1beta, Immunology, Biology, medicine.disease_cause, Hemolysin Proteins, Biochemistry, Microbiology, Streptococcus agalactiae, 03 medical and health sciences, Mice, 0302 clinical medicine, Bacterial Proteins, Cell Signaling, Phagosomes, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Humans, Molecular Biology, reproductive and urinary physiology, 030304 developmental biology, Phagosome, 0303 health sciences, Innate immune system, integumentary system, Macrophages, RNA, Interleukin, Inflammasome, Cell Biology, bacterial infections and mycoses, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Innate Immunity, RNA, Bacterial, Cytokine, bacteria, Carrier Proteins, Lysosomes, 030215 immunology, medicine.drug, Reports
Abstract

International audience; The inflammatory cytokine IL-1β is critical for host responses against many human pathogens. Here, we define Group B Streptococcus (GBS)-mediated activation of the Nod-like receptor-P3 (NLRP3) inflammasome in macrophages. NLRP3 activation requires GBS expression of the cytolytic toxin, β-hemolysin, lysosomal acidification, and leakage. These processes allow the interaction of GBS RNA with cytosolic NLRP3. The present study supports a model in which GBS RNA, along with lysosomal components including cathepsins, leaks out of lysosomes and interacts with NLRP3 to induce IL-1β production.

Published
2014
Full Text
View/download PDF

11. Activation of the NLRP3 inflammasome by group B streptococci

Author

Francesco Cardile, Giuseppe Mancuso, Giuseppe Teti, Giacomo Signorino, Patrick Trieu-Cuot, Antonio Malara, Angelina Midiri, Rahul Gupta, Douglas T. Golenbock, Carmelo Biondo, Roberta Galbo, Philipp Henneke, Concetta Beninati, Alessandro Costa, Salvatore Papasergi, Elie Metchnikoff Laboratory, University of Messina, Division of Infectious Diseases and Immunology, University of Massachusetts Medical School [Worcester] (UMASS), University of Massachusetts System (UMASS)-University of Massachusetts System (UMASS), Biologie des Bactéries pathogènes à Gram-positif, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany, This work was supported by a PRIN grant from MIUR of Italy, a PRA grant from the University of Messina, Bundesministerium fur Bildung und Forschung Grant BMBF 01 EO 0803, Deutsche Forschungsgemeinschaft Grants HE 3127/3-1 and 5-1, and National Institutes of Health Grant ROI AI052455-06A1 (to D.T.G.)., and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Inflammasomes, Interleukin-1beta, Immunology, Caspase 1, Biology, medicine.disease_cause, Pyrin domain, Article, Virulence factor, Streptococcus agalactiae, Microbiology, GBS, Inflammasome, cytokines, Hemolysin Proteins, Mice, 03 medical and health sciences, 0302 clinical medicine, Bacterial Proteins, Streptococcal Infections, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Immunology and Allergy, RNA, Messenger, 030304 developmental biology, Mice, Knockout, 0303 health sciences, Macrophages, Interleukin-18, Dendritic Cells, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Toll-Like Receptor 2, 3. Good health, CARD Signaling Adaptor Proteins, Mice, Inbred C57BL, Cytoskeletal Proteins, TLR2, Myeloid Differentiation Factor 88, Female, Signal transduction, Apoptosis Regulatory Proteins, Carrier Proteins, Signal Transduction, 030215 immunology, medicine.drug
Abstract

Group B Streptococcus (GBS) is a frequent agent of life-threatening sepsis and meningitis in neonates and adults with predisposing conditions. We tested the hypothesis that activation of the inflammasome, an inflammatory signaling complex, is involved in host defenses against this pathogen. We show in this study that murine bone marrow-derived conventional dendritic cells responded to GBS by secreting IL-1β and IL-18. IL-1β release required both pro–IL-1β transcription and caspase-1–dependent proteolytic cleavage of intracellular pro–IL-1β. Dendritic cells lacking the TLR adaptor MyD88, but not those lacking TLR2, were unable to produce pro–IL-1β mRNA in response to GBS. Pro–IL-1β cleavage and secretion of the mature IL-1β form depended on the NOD-like receptor family, pyrin domain containing 3 (NLRP3) sensor and the apoptosis-associated speck-like protein containing a caspase activation and recruitment domain adaptor. Moreover, activation of the NLRP3 inflammasome required GBS expression of β-hemolysin, an important virulence factor. We further found that mice lacking NLRP3, apoptosis-associated speck-like protein, or caspase-1 were considerably more susceptible to infection than wild-type mice. Our data link the production of a major virulence factor by GBS with the activation of a highly effective anti-GBS response triggered by the NLRP3 inflammasome.

Published
2012
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results