title: Fc gamma receptors regulate immune activation and susceptibility during Mycobacterium tuberculosis infection.
abstract: The critical role of cellular immunity during tuberculosis (TB) has been extensively studied, but the impact of Abs upon this infection remains poorly defined. Previously, we demonstrated that B cells are required for optimal protection in Mycobacterium tuberculosis-infected mice. FcgammaR modulate immunity by engaging Igs produced by B cells. We report that C57BL/6 mice deficient in inhibitory FcgammaRIIB (RIIB-/-) manifested enhanced mycobacterial containment and diminished immunopathology compared with wild-type controls. These findings corresponded with enhanced pulmonary Th1 responses, evidenced by increased IFN-gamma-producing CD4+ T cells, and elevated expression of MHC class II and costimulatory molecules B7-1 and B7-2 in the lungs. Upon M. tuberculosis infection and immune complex engagement, RIIB-/- macrophages produced more of the p40 component of the Th1-promoting cytokine IL-12. These data strongly suggest that FcgammaRIIB engagement can dampen the TB Th1 response by attenuating IL-12p40 production or activation of APCs. Conversely, C57BL/6 mice lacking the gamma-chain shared by activating FcgammaR had enhanced susceptibility and exacerbated immunopathology upon M. tuberculosis challenge, associated with increased production of the immunosuppressive cytokine IL-10. Thus, engagement of distinct FcgammaR can divergently affect cytokine production and susceptibility during M. tuberculosis infection.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Maglione
authors.forename: Jiayong
authors.initials: J
authors.lastname: Xu
authors.forename: Arturo
authors.initials: A
authors.lastname: Casadevall
authors.forename: John
authors.initials: J
authors.lastname: Chan
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics / Q000276:immunology / Q000517:prevention & control; D002478:Cells, Cultured; D004198:Disease Susceptibility / Q000276:immunology*; D005260:Female; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D017452:Receptors, IgG / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control
chemical_list: C499172:Fcgr2b protein, mouse; D017452:Receptors, IgG