3 369

Cited 34 times in

Mycobacterium tuberculosis RpfB drives Th1-type T cell immunity via a TLR4-dependent activation of dendritic cells

 Jong-Seok Kim  ;  Woo Sik Kim  ;  Han-Gyu Choi  ;  Byungki Jang  ;  Keehoon Lee  ;  Jong-Hwan Park  ;  Hwa-Jung Kim  ;  Sang-Nae Cho  ;  Sung Jae Shin 
 JOURNAL OF LEUKOCYTE BIOLOGY, Vol.94(4) : 733-749, 2013 
Journal Title
Issue Date
Animals ; Bacterial Proteins/metabolism* ; CD4-Positive T-Lymphocytes/cytology ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/cytology ; CD8-Positive T-Lymphocytes/metabolism ; Cell Death ; Cell Differentiation/immunology ; Cytokines/metabolism ; Dendritic Cells/cytology ; Dendritic Cells/immunology* ; Endotoxins/metabolism ; Enzyme Activation ; Female ; Immunity, Cellular/immunology* ; Immunologic Memory ; Mice ; Mitogen-Activated Protein Kinases/metabolism ; Mycobacterium tuberculosis/immunology* ; NF-kappa B/metabolism ; Neutralization Tests ; Phenotype ; Protein Binding ; Reproducibility of Results ; Sequence Deletion/genetics ; Signal Transduction/immunology ; Th1 Cells/cytology ; Th1 Cells/immunology* ; Toll-Like Receptor 2/metabolism ; Toll-Like Receptor 4/metabolism*
GATA-3 ; T-bet ; Vaccine
The failure of Mycobacterium bovis BCG as a TB vaccine against TB reactivation suggests that latency-associated proteins should be included in alternative TB vaccine development. Further, antigens known to generate protective immunity against the strong Th1 stimulatory response to reactivated TB should be included in novel vaccine design. Recent studies have emphasized the importance of Rpfs from Mycobacterium tuberculosis in the reactivation process and cellular immunity. However, little is known about how RpfB mediates protective immunity against M. tuberculosis. Here, we investigated the functional roles and signaling mechanisms of RpfB in DCs and its implications in the development of T cell immunity. DCs treated with RpfB displayed features of mature and functional status, with elevated 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). Activation of DCs was mediated by direct binding of RpfB to TLR4, followed by MyD88/TRIF-dependent signaling to MAPKs and NF-κB signaling pathways. Specifically, we found that the RpfB G5 domain is the most important part in RpfB binding to TLR4. RpfB-treated DCs effectively polarized naïve CD4(+) and CD8(+) T cells to secrete IFN-γ and IL-2. Importantly, RpfB induced the expansion of memory CD4(+)/CD8(+)CD44(high)CD62L(low) T cells in the spleen of M. tuberculosis-infected mice. Our data suggest that RpfB regulates innate immunity and activates adaptive immunity through TLR4, a finding that may help in the design of more effective vaccines.
Full Text
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
Lee, Kee Hoon(이기훈)
Jang, Byung Ki(장병기)
Cho, Sang Nae(조상래)
사서에게 알리기


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