title: TLR2 contributes to trigger immune response of pleural mesothelial cells against Mycobacterium bovis BCG and M. tuberculosis infection.
abstract: Mycobacterium tuberculosis is a causative agent leading to pleural effusion, characterized by the accumulation of fluid and immune cells in the pleural cavity. Although this phenomenon has been described before, detailed processes or mechanisms associated with the pleural effusion are still not well understood. Pleural mesothelial cells (PMCs) are specialized epithelial cells that cover the body wall and internal organs in pleural cavity playing a central role in pleural inflammation. Toll-like receptors are expressed in various cell types including mesothelial cells and initiate the recognition and defense against mycobacterial infection. In the present study, we investigated direct immune responses of PMCs against two mycobacterial strains, M. bovis vaccine strain Bacille Calmette-Guérin (BCG) and M. tuberculosis virulent strain H37Rv, and the role of TLR2 in such responses. Infection with BCG and H37Rv increased the production of IL-6, CXCL1, and CCL2 in WT PMCs, which was partially impaired in TLR2-deficient cells. In addition, the activation of NF-κB and MAPKs induced by BCG and H37Rv was suppressed in TLR2-deficient PMCs, as compared with the WT cells. TLR2 deficiency led to the decrease of nitric oxide (NO) production through the delayed gene expression of iNOS in PMCs. TLR2 was also shown to be essential for optimal expression of cellular adhesion molecules such as ICAM-1 and VCAM-1 in PMCs in response to BCG and H37Rv. These findings strongly suggest that TLR2 participates in mycobacteria-induced innate immune responses in PMCs and may play a role in pathogenesis of tuberculosis pleural effusion.
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju 61186, Republic of Korea; National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 28116, Republic of Korea.
authors.forename: Eun-Ha
authors.initials: EH
authors.lastname: Hwanga
authors.affiliation: Department of Microbiology and Immunology, David H. Smith Center for Vaccine Biology and Immunology, University of Rochester, Rochester, NY 14642, USA.
authors.forename: Tae-Hyoun
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju 61186, Republic of Korea.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Park
authors.affiliation: National Primate Research Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk 28116, Republic of Korea.
authors.forename: Jung Joo
authors.initials: JJ
authors.lastname: Hong
authors.affiliation: Center for Integrative Rheumatoid Transcriptomics and Dynamics, The Catholic University, Seoul 06591, Republic of Korea.
authors.forename: Dong-Hyun
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul 03722, Republic of Korea.
authors.forename: Sang-Jun
authors.initials: SJ
authors.lastname: Ha
authors.affiliation: School of Bioresources and Bioscience, Chung-Ang University, Anseong 456-756, Republic of Korea.
authors.forename: Soo-Jin
authors.initials: SJ
authors.lastname: Yang
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 03722, Republic of Korea.
authors.forename: Sung Jae
authors.initials: SJ
authors.lastname: Shin
authors.affiliation: Laboratory Animal Medicine, College of Veterinary Medicine and BK 21 PLUS Project Team, Chonnam National University, Gwangju 61186, Republic of Korea. Electronic address: jonpark@jnu.ac.kr.
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Park
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D004847:Epithelial Cells / Q000201:enzymology / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate; D008810:Mice, Inbred C57BL; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009163:Mycobacterium bovis; D009169:Mycobacterium tuberculosis; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis; D010994:Pleura / Q000166:cytology*; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000378:metabolism / Q000502:physiology*
chemical_list: D015815:Cell Adhesion Molecules; D018925:Chemokines; D016207:Cytokines; D016328:NF-kappa B; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D020929:Mitogen-Activated Protein Kinase Kinases
keywords: Innate immune response; Mycobacterium tuberculosis; Pleural mesothelial cells; TLR2