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

Authors
 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 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.287(46) : 38609-38624, 2012 
Journal Title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN
 0021-9258 
Issue Date
2012
MeSH
Animals ; Bacterial Proteins/metabolism ; Dendritic Cells/cytology ; Female ; Immune System ; Immunologic Memory ; Interferon-gamma/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Models, Biological ; Multienzyme Complexes/genetics* ; Multienzyme Complexes/physiology ; Mycobacterium avium subsp. paratuberculosis/metabolism* ; Nucleotidyltransferases/genetics* ; Nucleotidyltransferases/physiology ; Pentosyltransferases/genetics* ; Pentosyltransferases/physiology ; Recombinant Proteins/chemistry ; T-Lymphocytes/immunology ; Th1 Cells/cytology ; Toll-Like Receptor 4/metabolism
Keywords
Dendritic Cells ; Immunology ; Mycobacteria ; T Cell ; Toll-like Receptors (TLR) ; Memory T Cell ; Mycobacterium avium subsp. paratuberculosis ; Th1 Polarization ; Toll-like Receptor 4
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. MAP CobT recognizes TLR4, and induces DC maturation 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)CD62L(low) 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.
Full Text
http://www.jbc.org/content/287/46/38609.long
DOI
23019321
Appears in Collections:
1. College of Medicine (의과대학) > Research Institute (부설연구소) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Jong Seok(김종석)
Byun, Eui Hong(변의홍)
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
Lee, Kee Hoon(이기훈)
Cho, Sang Nae(조상래)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90626
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