Mycobacterium tuberculosis MmsA, a novel immunostimulatory antigen, induces dendritic cell activation and promotes Th1 cell-type immune responses.
Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis, is an outstanding pathogen that modulates the host immune response. This inconvenient truth drives the continual identification of antigens that generate protective immunity, including Th1-type T cell immunity. Here, the contribution of methylmalonate semialdehyde dehydrogenase (MmsA, Rv0753c) of Mtb to immune responses was examined in the context of dendritic cell (DC) activation and T cell immunity both in vitro and in vivo. The results showed that MmsA induced DC activation by activating the MAPK and NF-κB signaling pathways. Additionally, MmsA-treated DCs activated naïve T cells, effectively polarized CD4(+) and CD8(+) T cells to secrete IFN-γ and IL-2, and induced T cell proliferation. These results indicate that MmsA is a novel DC maturation-inducing antigen that drives the Th1 immune response. Thus, MmsA was found to potentially regulate immune responses via DC activation toward Th1-type T cell immunity, enhancing our understanding of Mtb pathogenesis.
Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
Jong-Seok
JS
Kim
Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
Woo Sik
WS
Kim
Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
Hong-Hee
HH
Choi
Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
Hong Min
HM
Kim
Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
Kee Woong
KW
Kwon
Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
Seung Jung
SJ
Han
Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
Seung Bin
SB
Cha
Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea.
Sang-Nae
SN
Cho
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, South Korea.
Won-Jung
WJ
Koh
Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, South Korea. Electronic address: sjshin@yuhs.ac.
Sung Jae
SJ
Shin
D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology; D001426:Bacterial Proteins / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000276:immunology; D050646:Methylmalonate-Semialdehyde Dehydrogenase (Acylating) / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism*; D018417:Th1 Cells / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D007376:Interleukin-2; D016328:NF-kappa B; D007371:Interferon-gamma; D050646:Methylmalonate-Semialdehyde Dehydrogenase (Acylating); D020928:Mitogen-Activated Protein Kinases
Dendritic cells; MAP kinase; MmsA; Mycobacterium tuberculosis; Th1-type immunity