BMB Rep. 2014; 47(2): 115-120  
The Mycobacterium avium subsp. Paratuberculosis protein MAP1305 modulates dendritic cell-mediated T cell proliferation through Toll-like receptor-4
Su Jung Lee1,#, Kyung Tae Noh3,#, Tae Heung Kang1, Hee Dong Han1, Sung Jae Shin4, Byoung Yul Soh5, Jung Hee Park6, Yong Kyoo Shin7, Han Wool Kim8, Cheol-Heui Yun8, Won Sun Park9, In Duk Jung1,* & Yeong-Min Park1,2,*
1Department of Immunology, Lab of Dendritic Cell Differentiation & Regulation, School of Medicine, Konkuk University, Chungju 380-701, 2Department of Microbiology and Immunology, School of Medicine, Pusan National University, Yangsan 626-770, 3Department of Infectious Diseases Research, Armed Forces Medical Research Institute, Daejeon 305-878, 4Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul 120-752, 5Department of Biochemistry, College of Medicine, Seonam University, Namwon 590-711, 6Division of Biotechnology, Advanced Institute of Environment and Bioscience, College of Environmental & Bioresources Sciences, Chonbuk National University, Iksan 570-752, 7Department of Pharmacology, Chung-Ang University, College of Medicine, Seoul 156-756, 8Department of Agricultural Biotechnology and Research Institute for Agriculture and Life Sciences, Seoul National University, Seoul 151-742, 9Department of Physiology, School of Medicine, Kangwon National University, Chuncheon 200-701, Korea
Correspondence to: In Duk Jung, Tel: +82-2-2049-6158; Fax: +82-2-2049-6192; E-mail: jungid@kku.ac.kr, Yeong-Min Park, Tel: +82-2-2049-6158; Fax: +82-2-2049-6192; E-mail: immun3023@kku.ac.kr
Received: December 10, 2013; Revised: December 16, 2013; Accepted: December 18, 2013; Published online: February 28, 2014.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

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 na?ve 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.
Keywords: Dendritic cells, MAPKs, MAP1305, Mycobacterium avium subsp. paratuberculosis, Th1 polarization


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