title: Tumor Necrosis Factor and Its Receptors Are Crucial to Control Mycobacterium bovis Bacillus Calmette-Guerin Pleural Infection in a Murine Model.
abstract: Tumor necrosis factor (TNF) is crucial to control Mycobacterium tuberculosis infection, which remains a leading cause of morbidity and mortality worldwide. TNF blockade compromises host immunity and may cause reactivation of latent infection, resulting in overt pulmonary, pleural, and extrapulmonary tuberculosis. Herein, we investigate the roles of TNF and TNF receptors in the control of Mycobacterium bovis bacillus Calmette-Guerin (BCG) pleural infection in a murine model. As controls, wild-type mice and those with a defective CCR5, a receptor that is crucial for control of viral infection but not for tuberculosis, were used. BCG-induced pleural infection was uncontrolled and progressive in absence of TNF or TNF receptor 1 (TNFR1)/TNFR2 (TNFR1R2) with increased inflammatory cell recruitment and bacterial load in the pleural cavity, and heightened levels of pleural and serum proinflammatory cytokines and chemokines, compared to wild-type control mice. The visceral pleura was thickened with chronic inflammation, which was prominent in TNF(-/-) and TNFR1R2(-/-) mice. The parietal pleural of TNF(-/-) and TNFR1R2(-/-) mice exhibited abundant inflammatory nodules containing mycobacteria, and these mice developed nonresolving inflammation and succumbed from disseminated BCG infection. By contrast, CCR5(-/-) mice survived and controlled pleural BCG infection as wild-type control mice. In conclusion, BCG-induced pleurisy was uncontrolled in the absence of TNF or TNF receptors with exacerbated inflammatory response, impaired bacterial clearance, and defective mesothelium repair, suggesting a critical role of TNF to control mycobacterial pleurisy.
authors.affiliation: Department of Pathology and Immunology, Centre Medical Universitaire, University of Geneva Medical School, Geneva, Switzerland; Laboratory of Integrative Immunology, National Institute of Respiratory Diseases Ismael Cosio Villegas, Mexico City, Mexico.
authors.forename: Leslie
authors.initials: L
authors.lastname: Chavez-Galan
authors.affiliation: Department of Pathology and Immunology, Centre Medical Universitaire, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Dominique
authors.initials: D
authors.lastname: Vesin
authors.affiliation: Experimental Molecular Immunology and Neurogenetics (UMR7355), University of Orléans and CNRS, Orléans, France.
authors.forename: Noria
authors.initials: N
authors.lastname: Segueni
authors.affiliation: Department of Pathology and Immunology, Centre Medical Universitaire, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Pritha
authors.initials: P
authors.lastname: Prasad
authors.affiliation: Department of Pathology and Immunology, Centre Medical Universitaire, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Raphaële
authors.initials: R
authors.lastname: Buser-Llinares
authors.affiliation: Department of Pathology and Immunology, Centre Medical Universitaire, University of Geneva Medical School, Geneva, Switzerland.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Blaser
authors.affiliation: Division of Clinical Pathology, University Hospital, Geneva, Switzerland.
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Pache
authors.affiliation: Experimental Molecular Immunology and Neurogenetics (UMR7355), University of Orléans and CNRS, Orléans, France.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ryffel
authors.affiliation: Experimental Molecular Immunology and Neurogenetics (UMR7355), University of Orléans and CNRS, Orléans, France.
authors.forename: Valérie F J
authors.initials: VF
authors.lastname: Quesniaux
authors.affiliation: Department of Pathology and Immunology, Centre Medical Universitaire, University of Geneva Medical School, Geneva, Switzerland. Electronic address: irene.garcia-gabay@unige.ch.
authors.forename: Irene
authors.initials: I
authors.lastname: Garcia
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009163:Mycobacterium bovis; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology*; D014396:Tuberculosis, Pleural / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha