title: The Mycobacterium avium subsp. Paratuberculosis protein MAP1305 modulates dendritic cell-mediated T cell proliferation through Toll-like receptor-4.
abstract: In this study, we show that Mycobacterium avium subsp. paratuberculosis MAP1305 induces the maturation of bone marrow-derived dendritic cells (BMDCs), a representative antigen presenting cell (APC). MAP1305 protein induces DC maturation and the production of pro-inflammatory cytokines (Interleukin (IL)-6), tumor necrosis factor (TNF)-α, and IL-1β) through Toll like receptor-4 (TLR-4) signaling by directly binding with TLR4. MAP1305 activates the phosphorylation of MAPKs, such as ERK, p38MAPK, and JNK, which is essential for DC maturation. Furthermore, MAP1305-treated DCs transform naïve T cells to polarized CD4(+) and CD8(+) T cells, thus indicating a key role for this protein in the Th1 polarization of the resulting immune response. Taken together, M. avium subsp. paratuberculosis MAP1305 is important for the regulation of innate immune response through DC-mediated proliferation of CD4(+) and CD8(+) T cells.
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju 380-701, Korea.
authors.forename: Su Jung
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Department of Infectious Diseases Research, Armed Forces Medical Research Institute, Daejeon 305-878, Korea.
authors.forename: Kyung Tae
authors.initials: KT
authors.lastname: Noh
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju 380-701, Korea.
authors.forename: Tae Heung
authors.initials: TH
authors.lastname: Kang
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju 380-701, Korea.
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Department of Biochemistry, College of Medicine, Seonam University, Namwon 590-711, Korea.
authors.forename: Byoung Yul
authors.initials: BY
authors.lastname: Soh
authors.affiliation: Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental & Bioresources Sciences, Chonbuk National University, Iksan 570-752, Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Pharmacology, Chung-Ang University, College of Medicine, Seoul 156-756, Korea.
authors.forename: Yong Kyoo
authors.initials: YK
authors.lastname: Shin
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Han Wool
authors.initials: HW
authors.lastname: Kim
authors.affiliation: Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Korea.
authors.forename: Cheol-Heui
authors.initials: CH
authors.lastname: Yun
authors.affiliation: Department of Physiology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea.
authors.forename: Won Sun
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju 380-701, Korea.
authors.forename: In Duk
authors.initials: ID
authors.lastname: Jung
authors.affiliation: Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju 380-701, Korea; Department of Microbiology and Immunology, School of Medicine, Pusan National University, Yangsan 626-770, Korea.
authors.forename: Yeong-Min
authors.initials: YM
authors.lastname: Park
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016927:Mycobacterium avium subsp. paratuberculosis / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D053583:Interleukin-1beta; D015850:Interleukin-6; D011994:Recombinant Proteins; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha