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

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
DOIs
StatePublished - Mar 1 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Fcγ receptors regulate immune activation and susceptibility during Mycobacterium tuberculosis infection'. Together they form a unique fingerprint.

  • Cite this