Mycobacterium tuberculosis RpfB drives Th1-type T cell immunity via a TLR4-dependent activation of dendritic cells

Jong Seok Kim, Woo Sik Kim, Han Gyu Choi, Byungki Jang, Keehoon Lee, Jong Hwan Park, Hwa Jung Kim, Sang Nae Cho, Sung Jae Shin

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

The failure of Mycobacterium bovis BCG as a TB vaccine against TB reactivation suggests that latency-associated proteins should be included in alternative TB vaccine development. Further, antigens known to generate protective immunity against the strong Th1 stimulatory response to reactivated TB should be included in novel vaccine design. Recent studies have emphasized the importance of Rpfs from Mycobacterium tuberculosis in the reactivation process and cellular immunity. However, little is known about how RpfB mediates protective immunity against M. tuberculosis. Here, we investigated the functional roles and signaling mechanisms of RpfB in DCs and its implications in the development of T cell immunity. DCs treated with RpfB displayed features of mature and functional status, with elevated 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). Activation of DCs was mediated by direct binding of RpfB to TLR4, followed by MyD88/TRIF-dependent signaling to MAPKs and NF-κB signaling pathways. Specifically, we found that the RpfB G5 domain is the most important part in RpfB binding to TLR4. RpfB-treated DCs effectively polarized naïve CD4+ and CD8+ T cells to secrete IFN-γ and IL-2. Importantly, RpfB induced the expansion of memory CD4+/CD8+CD44highCD62Llow T cells in the spleen of M. tuberculosis-infected mice. Our data suggest that RpfB regulates innate immunity and activates adaptive immunity through TLR4, a finding that may help in the design of more effective vaccines.

Original languageEnglish
Pages (from-to)733-749
Number of pages17
JournalJournal of Leukocyte Biology
Volume94
Issue number4
DOIs
Publication statusPublished - 2013 Oct

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Cell Biology

Fingerprint Dive into the research topics of 'Mycobacterium tuberculosis RpfB drives Th1-type T cell immunity via a TLR4-dependent activation of dendritic cells'. Together they form a unique fingerprint.

  • Cite this