Mycobacterium paratuberculosis CobT activates dendritic cells via engagement of toll-like receptor 4 resulting in Th1 cell expansion

Eui Hong Byun, Woo Sik Kim, Jong Seok Kim, Choul Jae Won, Han Gyu Choi, Hwa Jung Kim, Sang Nae Cho, Keehoon Lee, Tiejun Zhang, Gang Min Hur, Sung Jae Shin

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of Johne disease in animals and MAP involvement in human Crohn disease has been recently emphasized. Evidence from M. tuberculosis studies suggests mycobacterial proteins activate dendritic cells (DCs) via Toll-like receptor (TLR) 4, eventually determining the fate of immune responses. Here, we investigated whether MAP CobT contributes to the development of T cell immunity through the activation of DCs. MAPCobT recognizes TLR4, and inducesDCmaturation and activation via the MyD88 and TRIF signaling cascades, which are followed by MAP kinases and NF-κB. We further found that MAP CobT-treated DCs activated naive T cells, effectively polarized CD4+ and CD8 + T cells to secrete IFN-γ and IL-2, but not IL-4 and IL-10, and induced T cell proliferation. These data indicate that MAP CobT contributes to T helper (Th) 1 polarization of the immune response. MAP CobT-treated DCs specifically induced the expansion of CD4+/ CD8+ CD44 high CD62Llow memory T cells in the mesenteric lymph node of MAP-infected mice in a TLR4-dependent manner. Our results indicate that MAP CobT is a novel DC maturation-inducing antigen that drives Th1 polarized-naive/ memory T cell expansion in a TLR4-dependent cascade, suggesting that MAP CobT potentially links innate and adaptive immunity against MAP.

Original languageEnglish
Pages (from-to)38609-38624
Number of pages16
JournalJournal of Biological Chemistry
Volume287
Issue number46
DOIs
Publication statusPublished - 2012 Nov 9

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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