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Mycobacterium tuberculosis RpfE promotes simultaneous Th1- and Th17-type T-cell immunity via TLR4-dependent maturation of dendritic cells

Authors
 Han-Gyu Choi  ;  Woo Sik Kim  ;  Yong Woo Back  ;  Hongmin Kim  ;  Kee Woong Kwon  ;  Jong-Seok Kim  ;  Sung Jae Shin  ;  Hwa-Jung Kim 
Citation
 EUROPEAN JOURNAL OF IMMUNOLOGY, Vol.45(7) : 1957-1971, 2015 
Journal Title
 EUROPEAN JOURNAL OF IMMUNOLOGY 
ISSN
 0014-2980 
Issue Date
2015
MeSH
Animals ; Bacterial Proteins/immunology* ; Cell Differentiation/immunology ; Cell Separation ; Cytokines/immunology* ; Dendritic Cells/immunology* ; Female ; Flow Cytometry ; Immunoblotting ; Immunoprecipitation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microscopy, Confocal ; Mycobacterium tuberculosis/immunology ; Th1 Cells/immunology* ; Th17 Cells/immunology* ; Toll-Like Receptor 4/immunology* ; Tuberculosis/immunology*
Keywords
Dendritic cell ; Mycobacterium tuberculosis ; Resuscitation-promoting factor E (RpfE) ; TLR ; Th1 polarization ; Th17 polarization
Abstract
Reciprocal induction of the Th1 and Th17 immune responses is essential for optimal protection against Mycobacterium tuberculosis (Mtb); however, only a few Mtb antigens are known to fulfill this task. A functional role for resuscitation-promoting factor (Rpf) E, a latency-associated member of the Rpf family, in promoting naïve CD4(+) T-cell differentiation toward both Th1 and Th17 cell fates through interaction with dendritic cells (DCs) was identified in this study. RpfE induces DC maturation by increasing expression of surface molecules and the production of IL-6, IL-1β, IL-23p19, IL-12p70, and TNF-α but not IL-10. This induction is mediated through TLR4 binding and subsequent activation of ERK, p38 MAPKs, and NF-κB signaling. RpfE-treated DCs effectively caused naïve CD4(+) T cells to secrete IFN-γ, IL-2, and IL-17A, which resulted in reciprocal expansions of the Th1 and Th17 cell response along with activation of T-bet and RORγt but not GATA-3. Furthermore, lung and spleen cells from Mtb-infected WT mice but not from TLR4(-/-) mice exhibited Th1 and Th17 polarization upon RpfE stimulation. Taken together, our data suggest that RpfE has the potential to be an effective Mtb vaccine because of its ability to activate DCs that simultaneously induce both Th1- and Th17-polarized T-cell expansion.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/eji.201445329/abstract
DOI
10.1002/eji.201445329
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
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/140595
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