TLR2 contributes to trigger immune response of pleural mesothelial cells against Mycobacterium bovis BCG and M. tuberculosis infection

• Published in: Cytokine (Philadelphia, Pa.) Vol. 95; pp. 80 - 87
• Main Authors: Hwanga, Eun-Ha, Kim, Tae-Hyoun, Park, Ji-Yeon, Hong, Jung Joo, Kim, Dong-Hyun, Ha, Sang-Jun, Yang, Soo-Jin, Shin, Sung Jae, Park, Jong-Hwan
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2017
• Subjects: Animals; Cell Adhesion Molecules - metabolism; Cells, Cultured; Chemokines - biosynthesis; Cytokines - biosynthesis; Epithelial Cells - enzymology; Epithelial Cells - immunology; Epithelial Cells - metabolism; Immunity, Innate; Innate immune response; Mice, Inbred C57BL; Mitogen-Activated Protein Kinase Kinases - metabolism; Mycobacterium bovis; Mycobacterium tuberculosis; NF-kappa B - metabolism; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - biosynthesis; Pleura - cytology; Pleural mesothelial cells; Signal Transduction; TLR2; Toll-Like Receptor 2 - metabolism; Toll-Like Receptor 2 - physiology; TBPE; JNK; BCG; PMC; PMCs; TIRAP; Mycobacterium tuberculosis; poly(I:C); EPTB; iNOS; TLR; TIR; TRIF; IRF; Pleural mesothelial cells; Innate immune response; MAP; TLR2
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2017.02.021

•M. tuberculosis induces cytokines and chemokines production in PMCs via TLR2.•M. tuberculosis activates NF-κB and MAPKs in PMCs via TLR2 signaling.•TLR2 is essential for iNOS expression in M. tuberculosis-infected PMCs.•TLR2 is critical for expression of surface molecules in M. tuberculosis-infected PMCs. 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.