title: Rv0315, a novel immunostimulatory antigen of Mycobacterium tuberculosis, activates dendritic cells and drives Th1 immune responses.
abstract: Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the most deadly infectious diseases, with approximately two million people dying of TB annually. An effective therapeutic method for activating dendritic cells (DCs) and driving Th1 immune responses would improve host defenses and further the development of a TB vaccine. Given the importance of DC maturation in eliciting protective immunity against TB, we investigated whether Rv0315, a newly identified Mtb antigen, can prompt DC maturation. We found that Rv0315 functionally activated DCs by augmenting the expression of the co-stimulatory molecules CD80 and CD86 as well as MHC class I/II molecules. Moreover, it increased DC secretion of the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α. Unlike LPS, however, Rv0315 induced the secretion of IL-12p70, but not IL-10. In addition, Rv0315-treated DCs accelerated the proliferation of CD4(+) and CD8(+) splenic T cells from Mtb-infected mice, with increased levels of IFN-γ, in syngeneic and allogeneic mixed lymphocyte reactions, indicating that Rv0315 contributes to Th1 polarization of the immune response. Importantly, both mitogen-activated protein kinases and nuclear factor κB signaling mediated the expression of DC surface markers and cytokines. Taken together, our results indicate that Rv0315 is a novel DC maturation-inducing antigen that drives T cell immune responses toward Th1 polarization, suggesting that Rv0315 plays a key role in determining the nature of the immune response to TB.
authors: Department of Microbiology and Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-747, South Korea.
authors: Eui-Hong
authors: EH
authors: Byun
authors: Woo Sik
authors: WS
authors: Kim
authors: A-Rum
authors: AR
authors: Shin
authors: Jong-Seok
authors: JS
authors: Kim
authors: Jake
authors: J
authors: Whang
authors: Choul-Jae
authors: CJ
authors: Won
authors: Yohan
authors: Y
authors: Choi
authors: Su-Young
authors: SY
authors: Kim
authors: Won Jung
authors: WJ
authors: Koh
authors: Hwa-Jung
authors: HJ
authors: Kim
authors: Sung Jae
authors: SJ
authors: Shin
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; C072681:Mycobacterium tuberculosis antigens; D007371:Interferon-gamma