title: Mycobacterium leprae-Infected Macrophages Preferentially Primed Regulatory T Cell Responses and Was Associated with Lepromatous Leprosy.
abstract: 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.
  
  
  RESULTS
  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
  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.
authors.affiliation: Shanghai Dermatology Hospital, Shanghai, P. R. China.
authors.forename: Degang
authors.initials: D
authors.lastname: Yang
authors.affiliation: Yunnan Center for Disease Control and Prevention, Kunming, P. R. China.
authors.forename: Tiejun
authors.initials: T
authors.lastname: Shui
authors.affiliation: Ian Therapeutics and Research Lab, Vancouver, British Columbia, Canada.
authors.forename: Jake W
authors.initials: JW
authors.lastname: Miranda
authors.affiliation: Ian Therapeutics and Research Lab, Vancouver, British Columbia, Canada.
authors.forename: Danny J
authors.initials: DJ
authors.lastname: Gilson
authors.affiliation: BGC Biotechnology Research Center, Shandong, P. R. China.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Song
authors.affiliation: Shanghai Dermatology Hospital, Shanghai, P. R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.affiliation: Shanghai Dermatology Hospital, Shanghai, P. R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Shi
authors.affiliation: Shanghai Dermatology Hospital, Shanghai, P. R. China.
authors.forename: Jianyu
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Yunnan Center for Disease Control and Prevention, Kunming, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Shanghai Dermatology Hospital, Shanghai, P. R. China.
authors.forename: Zhichun
authors.initials: Z
authors.lastname: Jing
mesh_terms: D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D018920:Coculture Techniques; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology / Q000502:physiology; D005802:Genes, MHC Class II / Q000502:physiology; D006801:Humans; D015440:Leprosy, Lepromatous / Q000276:immunology*; D008264:Macrophages / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*
chemical_list: D016207:Cytokines