title: Mycobacterium tuberculosis RpfE promotes simultaneous Th1- and Th17-type T-cell immunity via TLR4-dependent maturation of dendritic cells.
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.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.|Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Han-Gyu
authors.initials: HG
authors.lastname: Choi
authors.affiliation: Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Woo Sik
authors.initials: WS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Back
authors.affiliation: Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Kee Woong
authors.initials: KW
authors.lastname: Kwon
authors.affiliation: Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Jong-Seok
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Microbiology, Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.|Infection Signaling Network Research Center, College of Medicine, Chungnam National University, Daejeon, Republic of Korea.
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D002469:Cell Separation; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015151:Immunoblotting; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009169:Mycobacterium tuberculosis / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology*
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C113704:resuscitation-promoting factor, bacteria
keywords: Dendritic cell; Mycobacterium tuberculosis; Resuscitation-promoting factor E (RpfE); TLR; Th1 polarization; Th17 polarization