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 language | English |
|---|---|
| Pages (from-to) | 38609-38624 |
| Number of pages | 16 |
| Journal | Journal of Biological Chemistry |
| Volume | 287 |
| Issue number | 46 |
| DOIs | |
| Publication status | Published - 2012 Nov 9 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Molecular Biology
- Cell Biology
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Mycobacterium paratuberculosis CobT activates dendritic cells via engagement of toll-like receptor 4 resulting in Th1 cell expansion. / Byun, Eui Hong; Kim, Woo Sik; Kim, Jong Seok; Won, Choul Jae; Choi, Han Gyu; Kim, Hwa Jung; Cho, Sang Nae; Lee, Keehoon; Zhang, Tiejun; Hur, Gang Min; Shin, Sung Jae.
In: Journal of Biological Chemistry, Vol. 287, No. 46, 09.11.2012, p. 38609-38624.Research output: Contribution to journal › Article
TY - JOUR
T1 - Mycobacterium paratuberculosis CobT activates dendritic cells via engagement of toll-like receptor 4 resulting in Th1 cell expansion
AU - Byun, Eui Hong
AU - Kim, Woo Sik
AU - Kim, Jong Seok
AU - Won, Choul Jae
AU - Choi, Han Gyu
AU - Kim, Hwa Jung
AU - Cho, Sang Nae
AU - Lee, Keehoon
AU - Zhang, Tiejun
AU - Hur, Gang Min
AU - Shin, Sung Jae
PY - 2012/11/9
Y1 - 2012/11/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84869070342&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84869070342&partnerID=8YFLogxK
U2 - 10.1074/jbc.M112.391060
DO - 10.1074/jbc.M112.391060
M3 - Article
C2 - 23019321
AN - SCOPUS:84869070342
VL - 287
SP - 38609
EP - 38624
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 46
ER -