%0 Journal Article
%T Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy
%A Degang Yang&nbsp
%A Tiejun Shui&nbsp
%A Jake W. Miranda&nbsp
%A Danny J. Gilson&nbsp
%A Zhengyu Song&nbsp
%A Jia Chen&nbsp
%A Chao Shi&nbsp
%A Jianyu Zhu&nbsp
%A Jun Yang&nbsp
%A Zhichun Jing
%J PLOS Neglected Tropical Diseases
%D 2016
%I Public Library of Science (PLoS)
%R 10.1371/journal.pntd.0004335
%X 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.
%U http://www.plosntds.org/article/info%3Adoi%2F10.1371%2Fjournal.pntd.0004335