title: Mycobacterium tuberculosis Rv0577, a novel TLR2 agonist, induces maturation of dendritic cells and drives Th1 immune response.
abstract: Tuberculosis (TB) caused by Mycobacterium tuberculosis constitutes an ongoing threat to global health. An antigen that can induce dendritic cell (DC) maturation and lead to enhanced cellular immunity is crucial to the development of an effective TB vaccine. Here, we investigated the functional roles and the related signaling mechanism of the Rv0577 protein, a M. tuberculosis complex-restricted secreted protein involved in the methylglyoxal detoxification pathway. Rv0577 recognizes Toll-like receptor 2 (TLR2) and functionally induces DC maturation by augmenting the expression of cell surface molecules (CD80, CD86, and MHC class I and II) and proinflammatory cytokine production (TNF-α, IL-1β, IL-6, and IL-12p70) in DCs on MyD88-dependent signaling, mitogen-activated protein kinases, and nuclear factor κB signaling pathways. In addition, Rv0577-treated DCs activated naive T cells, effectively polarized CD4(+) and CD8(+) T cells to secrete IFN-γ and IL-2, and induced T-cell proliferation, indicating that this protein possibly contributes to Th1-polarization of the immune response. More important, unlike LPS, Rv0577-treated DCs specifically induced the proliferation of memory CD4(+)/CD8(+)CD44(high)CD62L(low) T cells in the spleen of M. tuberculosis-infected mice in a TLR2-dependent manner. Taken together, these findings suggest that Rv0577 may regulate innate and adaptive immunity by interacting with TLR2, a finding that could be helpful in the design of new TB vaccines.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors.forename: Eui-Hong
authors.initials: EH
authors.lastname: Byun
authors.forename: Woo Sik
authors.initials: WS
authors.lastname: Kim
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Kim
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001426:Bacterial Proteins / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D051195:Toll-Like Receptor 2 / Q000819:agonists*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; C480221:Cfp32 protein, Mycobacterium tuberculosis; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D014409:Tumor Necrosis Factor-alpha; D048049:Extracellular Signal-Regulated MAP Kinases