Immunoregulatory role of IFNγ in granulomas of Mycobacterium tuberculosis-infected rhesus macaques 3823

Abstract Description T cell-dependent control of Mycobacterium tuberculosis (Mtb) infection is thought to be primarily mediated by IFNγ, but local role of IFNγ in granulomas, the sites of bacterial replication in the lungs, is poorly understood. Here we examine the effects of IFNγ blockade in Mtb-infected rhesus macaques either before or after the establishment of granulomas. IFNγ blockade after granuloma formation increased IFNβ levels and multiple features of antiviral-like immune responses. In contrast, initiating IFNγ blockade upon infection reduced Mtb-specific CD8 T cells and promoted B cell accumulation in granulomas. Unexpectedly, three months of IFNγ blockade did not impact bacterial replication or disease manifestation. In fact, granulomas with the lowest levels of bioactive IFNγ after blockade contained the fewest bacteria. Thus, the beneficial effects of IFNγ during Mtb infection may in part result from inhibition of detrimental type I IFN responses. However, T cell-mediated resistance to tuberculosis may require IFNγ-independent effector functions not yet identified. Funding Sources This study was supported by the Intramural Research Program of the NIAID, NIH. Topic Categories Cytokines and Chemokines and Their Receptors (CCR)