Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy

Background The persistence of Mycobacterium leprae ( M . leprae ) infection is largely dependent on the types of host immune responses being induced. Macrophage, a crucial modulator of innate and adaptive immune responses, could be directly infected by M . leprae . We therefore postulated that M . leprae -infected macrophages might have altered immune functions. Methodology/Principal Findings Here, we treated monocyte-derived macrophages with live or killed M . leprae , and examined their activation status and antigen presentation. We found that macrophages treated with live M . leprae showed committed M2-like function, with decreased interleukin 1 beta (IL-1beta), IL-6, tumor necrosis factor alpha (TNF-alpha) and MHC class II molecule expression and elevated IL-10 and CD163 expression. When incubating with naive T cells, macrophages treated with live M . leprae preferentially primed regulatory T (Treg) cell responses with elevated FoxP3 and IL-10 expression, while interferon gamma (IFN-gamma) expression and CD8 + T cell cytotoxicity were reduced. Chromium release assay also found that live M . leprae -treated macrophages were more resistant to CD8 + T cell-mediated cytotoxicity than sonicated M . leprae -treated monocytes. Ex vivo studies showed that the phenotype and function of monocytes and macrophages had clear differences between L-lep and T-lep patients, consistent with the in vitro findings. Conclusions/Significance Together, our data demonstrate that M . leprae could utilize infected macrophages by two mechanisms: firstly, M . leprae -infected macrophages preferentially primed Treg but not Th1 or cytotoxic T cell responses; secondly, M . leprae -infected macrophages were more effective at evading CD8 + T cell-mediated cytotoxicity.