Rv0315, a novel immunostimulatory antigen of mycobacterium tuberculosis, activates dendritic cells and drives th1 immune responses

Eui Hong Byun, Woo Sik Kim, A. Rum Shin, Jong Seok Kim, Jake Whang, Choul Jae Won, Yohan Choi, Su Young Kim, Won Jung Koh, Hwa Jung Kim, Sung Jae Shin

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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 proinflammatory cytokines IL-6, IL-1β, and TNF-?. 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 Mtbinfected mice, with increased levels of IFN-g, 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 ?B 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.

Original languageEnglish
Pages (from-to)285-298
Number of pages14
JournalJournal of Molecular Medicine
Volume90
Issue number3
DOIs
Publication statusPublished - 2012 Mar 1

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All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery
  • Genetics(clinical)

Cite this

Byun, E. H., Kim, W. S., Shin, A. R., Kim, J. S., Whang, J., Won, C. J., Choi, Y., Kim, S. Y., Koh, W. J., Kim, H. J., & Shin, S. J. (2012). Rv0315, a novel immunostimulatory antigen of mycobacterium tuberculosis, activates dendritic cells and drives th1 immune responses. Journal of Molecular Medicine, 90(3), 285-298. https://doi.org/10.1007/s00109-011-0819-2