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2. Induction of CCL8/MCP-2 by Mycobacteria through the Activation of TLR2/PI3K/Akt Signaling Pathway

Author

Liu, Haipeng, Liu, Zhonghua, Chen, Jianxia, Chen, Ling, He, Xin, Zheng, Ruijuan, Yang, Hong, Song, Peng, Weng, Dong, Hu, Haili, Fan, Lin, Xiao, Heping, Kaufmann, Stefan HE, Ernst, Joel, and Ge, Baoxue

Subjects
Biochemistry and Cell Biology, Biomedical and Clinical Sciences, Biological Sciences, Rare Diseases, Infectious Diseases, Emerging Infectious Diseases, Tuberculosis, Infection, Good Health and Well Being, Adult, Animals, Cell Line, Cell Line, Tumor, Cells, Cultured, Chemokine CCL8, Female, Host-Pathogen Interactions, Humans, Immunoblotting, Macrophages, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Middle Aged, Mycobacterium bovis, Mycobacterium tuberculosis, Phosphatidylinositol 3-Kinases, Phosphoinositide-3 Kinase Inhibitors, Pleural Effusion, Proto-Oncogene Proteins c-akt, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction, Toll-Like Receptor 2, Tuberculosis, Pleural, General Science & Technology
Abstract

Pleural tuberculosis (TB), together with lymphatic TB, constitutes more than half of all extrapulmonary cases. Pleural effusions (PEs) in TB are representative of lymphocytic PEs which are dominated by T cells. However, the mechanism underlying T lymphocytes homing and accumulation in PEs is still incompletely understood. Here we performed a comparative analysis of cytokine abundance in PEs from TB patients and non-TB patients by protein array analysis and observed that MCP-2/CCL8 is highly expressed in the TB-PEs as compared to peripheral blood. Meanwhile, we observed that CCR5, the primary receptor used by MCP-2/CCL8, is mostly expressed on pleural CD4(+) T lymphocytes. Furthermore, we found that infection with either Mycobacterium bovis Bacillus Calmette-Guérin (BCG) or Mycobacterium tuberculosis H37Rv induced production of MCP-2/CCL8 at both transcriptional and protein level in Raw264.7 and THP-1 macrophage cells, mouse peritoneal macrophages as well as human PBMC monocyte-derived macrophages (MDMs). The induction of MCP-2/CCL8 by mycobacteria is dependent on the activation of TLR2/PI3K/Akt and p38 signaling pathway. We conclude that accumulation of MCP-2/CCL8 in TB-PEs may function as a biomarker for TB diagnosis.

Published
2013

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