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. © 2016 yang et al.