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Mycobacterium tuberculosis Rv0577, a novel TLR2 agonist, induces maturation of dendritic cells and drives Th1 immune response.

Authors
 Eui-Hong Byun  ;  Woo Sik Kim  ;  Jong-Seok Kim  ;  In Duk Jung  ;  Yeong-Min Park  ;  Hwa-Jung Kim  ;  Sang-Nae Cho  ;  Sung Jae Shin 
Citation
 FASEB Journal, Vol.26(6) : 2695-2711, 2012 
Journal Title
 FASEB Journal 
ISSN
 0892-6638 
Issue Date
2012
MeSH
Adaptive Immunity ; Animals ; Bacterial Proteins/pharmacology* ; Cell Proliferation/drug effects* ; Dendritic Cells/cytology ; Dendritic Cells/drug effects* ; Dendritic Cells/metabolism ; Extracellular Signal-Regulated MAP Kinases/biosynthesis ; Female ; Interleukin-1beta/secretion ; Interleukin-6/secretion ; Mice ; NF-kappa B/biosynthesis ; Th1 Cells/drug effects ; Th1 Cells/immunology* ; Toll-Like Receptor 2/agonists* ; Tumor Necrosis Factor-alpha/secretion
Keywords
Toll-like receptor ; tuberculosis ; surface molecules ; proinflammatory cytokines ; memory T cell
Abstract
Tuberculosis (TB) caused by Mycobacterium tuberculosis constitutes an ongoing threat to global health. An antigen that can induce dendritic cell (DC) maturation and lead to enhanced cellular immunity is crucial to the development of an effective TB vaccine. Here, we investigated the functional roles and the related signaling mechanism of the Rv0577 protein, a M. tuberculosis complex-restricted secreted protein involved in the methylglyoxal detoxification pathway. Rv0577 recognizes Toll-like receptor 2 (TLR2) and functionally induces DC maturation by augmenting the 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) in DCs on MyD88-dependent signaling, mitogen-activated protein kinases, and nuclear factor κB signaling pathways. In addition, Rv0577-treated DCs activated naive T cells, effectively polarized CD4(+) and CD8(+) T cells to secrete IFN-γ and IL-2, and induced T-cell proliferation, indicating that this protein possibly contributes to Th1-polarization of the immune response. More important, unlike LPS, Rv0577-treated DCs specifically induced the proliferation of memory CD4(+)/CD8(+)CD44(high)CD62L(low) T cells in the spleen of M. tuberculosis-infected mice in a TLR2-dependent manner. Taken together, these findings suggest that Rv0577 may regulate innate and adaptive immunity by interacting with TLR2, a finding that could be helpful in the design of new TB vaccines.
Files in This Item:
T201201888.pdf Download
DOI
22415304
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
5. Research Institutes (연구소) > Institute for Immunology and Immunological Disease (면역질환연구소) > 1. Journal Papers
Yonsei Authors
Kim, Jong Seok(김종석)
Shin, Sung Jae(신성재) ORCID logo https://orcid.org/0000-0003-0854-4582
Cho, Sang Nae(조상래)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/90290
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