Myeloid cell TNFR1 signaling dependent liver injury and inflammation upon BCG infection

Article Article scientifique Article Myeloid cell TNFR1 signaling dependent liver injury and inflammation upon BCG infection eng 2019-03-28 author Chavez Galan Leslie 0000-0002-2334-0361 Department of Pathology and Immunology, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, Geneva, 1211, Switzerland.,Laboratory of Integrative Immunology, National Institute of Respiratory Diseases "Ismael Cosio Villegas", Mexico City, 14080, Mexico. 814837 author Vesin Marie-Dominique Department of Pathology and Immunology, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, Geneva, 1211, Switzerland. 65117 author Blaser Guillaume Department of Pathology and Immunology, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, Geneva, 1211, Switzerland. 583057 author Uysal Husnu Department of Pathology and Immunology, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, Geneva, 1211, Switzerland. 646577 immatriculations et bourses stand. (IMMAT) author Benmerzoug Sulayman CNRS, UMR7355, Orleans, France.,Experimental and Molecular Immunology and Neurogenetics, University of Orléans, Orléans, France. author Rose Stéphanie CNRS, UMR7355, Orleans, France.,Experimental and Molecular Immunology and Neurogenetics, University of Orléans, Orléans, France. author Ryffel Bernhard CNRS, UMR7355, Orleans, France.,Experimental and Molecular Immunology and Neurogenetics, University of Orléans, Orléans, France. author Quesniaux Valérie F J 0000-0003-2907-7995 CNRS, UMR7355, Orleans, France.,Experimental and Molecular Immunology and Neurogenetics, University of Orléans, Orléans, France. author Garcia Irène Department of Pathology and Immunology, Centre Medical Universitaire (CMU), Faculty of Medicine, University of Geneva, Geneva, 1211, Switzerland. Irene.Garcia-Gabay@unige.ch. 26048 5297 10.1038/s41598-019-41629-9 30923339 2045-2322 PMC6438980 https://www.nature.com/articles/s41598-019-41629-9 TNF plays a critical role in mononuclear cell recruitment during acute Bacillus Calmette-Guérin (BCG) infection leading to an effective immune response with granuloma formation, but may also cause tissue injury mediated by TNFR1 or TNFR2. Here we investigated the role of myeloid and T cell specific TNFR1 and R2 expression, and show that absence of TNFR1 in myeloid cells attenuated liver granuloma formation and liver injury in response to acute BCG infection, while TNFR2 expressed in myeloid cells contributed only to liver injury. TNFR1 was the main receptor controlling cytokine production by liver mononuclear cells after antigenic specific response, modified CD4/CD8 ratio and NK, NKT and regulatory T cell recruitment. Further analysis of CD11b<sup>+</sup> CD3<sup>+</sup> phagocytic cells revealed a TCRαβ expressing subpopulation of unknown function, which increased in response to BCG infection dependent of TNFR1 expression on myeloid cells. In conclusion, TNFR1 expressed by myeloid cells plays a critical role in mononuclear cell recruitment and injury of the liver after BCG infection. Animals BCG Vaccine / adverse effects BCG Vaccine / immunology Cytokines / immunology Cytokines / metabolism Disease Models, Animal Granuloma / immunology Granuloma / microbiology Granuloma / pathology Hepatitis / immunology Hepatitis / microbiology Hepatitis / pathology Humans Liver / cytology Liver / immunology Liver / pathology Mice Mice, Knockout Mycobacterium bovis / immunology Mycobacterium bovis / pathogenicity Myeloid Cells / immunology Myeloid Cells / metabolism Receptors, Antigen, T-Cell, alpha-beta / metabolism Receptors, Tumor Necrosis Factor, Type I / genetics Receptors, Tumor Necrosis Factor, Type I / metabolism Receptors, Tumor Necrosis Factor, Type II / genetics Receptors, Tumor Necrosis Factor, Type II / metabolism Signal Transduction / immunology T-Lymphocytes, Regulatory / immunology T-Lymphocytes, Regulatory / metabolism Vaccines, Live, Unattenuated / adverse effects Dewey 616.07 Swiss National Science Foundation Roles of TNF receptors in immunoregulation of responses to mycobacterial infections 146833 CH 137 Département de pathologie et immunologie 21F false Scientific reports 9 1 6099a3e4-6929-4695-8ea9-5b28053620f6 Article (Published version) Public Article_scientifique_from_crossref.pdf 3958285 application/pdf CC BY-4.0 f4d7abbd16e8a26dde83ccb0bb3fb74d366c9faa35c7808fe9133d4f65dfd127 9e59d64c-9087-4f92-ac16-350fc58d6ffc Supplemental data Public 41598_2019_41629_MOESM1_ESM.pdf 1238906 application/pdf e98ddb2c25b395889a910cf32029575e3dedd05aa43cd187e5c4910241bcc1b7 openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

Title	Published in	Year	Views	Downloads

Myeloid cell TNFR1 signaling dependent liver injury and inflammation upon BCG infection	Scientific reports	2019	5	5
Transmembrane Tumor Necrosis Factor Controls Myeloid-Derived Suppressor Cell Activity via TNF Receptor 2 and Protects from Excessive Inflammation during BCG-Induced Pleurisy	Frontiers in Immunology	2017	456	287

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