0 66

Cited 2 times in

A novel Th1-type T-cell immunity-biasing effect of malate dehydrogenase derived from Mycobacterium avium subspecies paratuberculosis via the activation of dendritic cells

Authors
 Woo Sik Kim  ;  Jong-Seok Kim  ;  Min-Kyoung Shin  ;  Sung Jae Shin 
Citation
 Cytokine, Vol.104 : 14-22, 2018 
Journal Title
 Cytokine 
ISSN
 1043-4666 
Issue Date
2018
Keywords
Dendritic cells ; Malate dehydrogenase ; Maturation ; Mycobacterium avium subsp. paratuberculosis ; Th1 polarization
Abstract
Mycobacterium avium subspecies paratuberculosis (MAP) is the causative pathogen of Johne's disease in ruminants, characterized by chronic granulomatous enteritis; it also has zoonotic potential and is associated with Crohn's disease in humans. A better understanding of the mycobacterial antigens and their roles in the host immune response may facilitate the rational design of control strategies, including the development of effective vaccines and diagnostic tools. However, the functional roles of a large proportion of MAP antigens involved in modulating the host immune response remain unknown. In this study, an immunological role of MAP malate dehydrogenase (MDH, MAP2541c), an antigen that is upregulated in stress culture conditions, such as nutrient starvation and hypoxia, in polarizing naive CD4(+)/CD8(+) T cells toward Th1-biased T-cell immunity via the activation of dendritic cells (DCs) was identified. DCs treated with MAP MDH displayed characteristics of the activated and mature immune status, with augmented expression of cell surface molecules and pro-inflammatory cytokines, including TNF-alpha, IL-1beta, IL-6, and IL-12p70, but not IL-10, along with a dose-dependent decrease in the antigen uptake capacity. A mechanistic investigation revealed that the observed DC maturation is mediated by the activation of JNK, ERK, and p38 MAP kinases, and the NF-kappaB signaling pathway. Notably, DCs activated by MAP MDH treatment promoted naive CD4(+)/CD8(+) T cell proliferation; in particular, they effectively polarized naive CD4(+) T cells to secrete IFN-gamma and IL-2 and activate T-bet, but, unlike the LPS control, did not influence IL-5 and GATA-3. These results indicated that MAP MDH has the potential to induce the Th1 cell response via DC activation. Collectively, our data demonstrated that MAP MDH is a novel immunostimulatory antigen that drives Th1-biased T cell polarization via interactions with DCs, suggesting that MDP MDH has the potential to be an effective MAP vaccine antigen target and diagnostic marker.
Full Text
https://www.sciencedirect.com/science/article/pii/S1043466618300358
DOI
10.1016/j.cyto.2018.01.022
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실)
Yonsei Authors
신성재(Shin, Sung Jae)
Export
RIS (EndNote)
XLS (Excel)
XML
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/162278
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse