Fcγ receptors regulate immune activation and susceptibility during Mycobacterium tuberculosis infection

Paul J. Maglione, Jiayong Xu, Arturo Casadevall, John Chan

Research output: Contribution to journalArticle

94 Citations (Scopus)

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. FcγR modulate immunity by engaging Igs produced by B cells. We report that C57BL/6 mice deficient in inhibitory FcγRIIB (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-γ-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 FcγRIIB engagement can dampen the TB Th1 response by attenuating IL-12p40 production or activation of APCs. Conversely, C57BL/6 mice lacking the γ-chain shared by activating FcγR had enhanced susceptibility and exacerbated immunopathology upon M. tuberculosis challenge, associated with increased production of the immunosuppressive cytokine IL-10. Thus, engagement of distinct FcγR can divergently affect cytokine production and susceptibility during M. tuberculosis infection.

Original languageEnglish (US)
Pages (from-to)3329-3338
Number of pages10
JournalJournal of Immunology
Volume180
Issue number5
StatePublished - Mar 1 2008

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Mycobacterium Infections
Fc Receptors
Mycobacterium tuberculosis
Cytokines
Inbred C57BL Mouse
Tuberculosis
B-Lymphocytes
CD80 Antigens
Interleukin-12 Subunit p40
Lung
Interleukin-12
Immunosuppressive Agents
Antigen-Antibody Complex
Cellular Immunity
Interleukin-10
Immunity
Macrophages
T-Lymphocytes
Infection

ASJC Scopus subject areas

  • Immunology

Cite this

Fcγ receptors regulate immune activation and susceptibility during Mycobacterium tuberculosis infection. / Maglione, Paul J.; Xu, Jiayong; Casadevall, Arturo; Chan, John.

In: Journal of Immunology, Vol. 180, No. 5, 01.03.2008, p. 3329-3338.

Research output: Contribution to journalArticle

Maglione, Paul J. ; Xu, Jiayong ; Casadevall, Arturo ; Chan, John. / Fcγ receptors regulate immune activation and susceptibility during Mycobacterium tuberculosis infection. In: Journal of Immunology. 2008 ; Vol. 180, No. 5. pp. 3329-3338.
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