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Fc Receptors Regulate Immune Activation and Susceptibility during Mycobacterium tuberculosis Infection¹

Paul J. Maglione^*, Jiayong Xu, Arturo Casadevall^*, and John Chan^2,*,

^* Department of Microbiology and Immunology and Department of Medicine, Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY 10461

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

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by National Institutes of Health Grants R01 HL071241, R01 AI50732, P01 AI063537, and Albert Einstein College of Medicine/Montefiore Medical Center for AIDS Research Grants P30 AI051519 (to J.C.), U54 AI05715805 and R01 AI03377414 (to A.C.), and T32 AI007506, and by a Seed grant from the American Medical Association Foundation (to P.J.M.). This work constitutes partial fulfillment of the thesis requirements for P.J.M. in the Graduate Division of Medical Sciences, Albert Einstein College of Medicine.

² Address correspondence and reprint requests to Dr. John Chan, Department of Medicine, Forchheimer Building 406, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461. E-mail address: jchan{at}aecom.yu.edu

³ Abbreviations used in this paper: TB, tuberculosis; PPD, mycobacterial purified protein derivative.

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The JI 2008 180: 2721-2722. [Full Text]