Induction of CCL8/MCP-2 by Mycobacteria through the Activation of TLR2/PI3K/Akt Signaling Pathway
Copyright policy )Induction of CCL8/MCP-2 by Mycobacteria through the Activation of TLR2/PI3K/Akt Signaling Pathway
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.
- New York University United States
- Tongji University China (People's Republic of)
- Max Planck Society Germany
- University of California, San Francisco United States
- Max Planck Institute for Infection Biology Germany
Male, Inbred C57BL, Mice, Phosphatidylinositol 3-Kinases, Chemokine CCL8, Cells, Cultured, Phosphoinositide-3 Kinase Inhibitors, Mice, Knockout, Tumor, Cultured, Reverse Transcriptase Polymerase Chain Reaction, Q, R, Biological Sciences, Middle Aged, Mycobacterium bovis, Infectious Diseases, Host-Pathogen Interactions, Medicine, Female, Infection, Pleural, Signal Transduction, Research Article, Adult, General Science & Technology, Cells, Knockout, Science, Immunoblotting, 610, Cell Line, Rare Diseases, Cell Line, Tumor, 616, Tuberculosis, Animals, Humans, Biomedical and Clinical Sciences, Macrophages, Mycobacterium tuberculosis, Toll-Like Receptor 2, Pleural Effusion, Mice, Inbred C57BL, Emerging Infectious Diseases, Good Health and Well Being, Biochemistry and Cell Biology, Proto-Oncogene Proteins c-akt
Male, Inbred C57BL, Mice, Phosphatidylinositol 3-Kinases, Chemokine CCL8, Cells, Cultured, Phosphoinositide-3 Kinase Inhibitors, Mice, Knockout, Tumor, Cultured, Reverse Transcriptase Polymerase Chain Reaction, Q, R, Biological Sciences, Middle Aged, Mycobacterium bovis, Infectious Diseases, Host-Pathogen Interactions, Medicine, Female, Infection, Pleural, Signal Transduction, Research Article, Adult, General Science & Technology, Cells, Knockout, Science, Immunoblotting, 610, Cell Line, Rare Diseases, Cell Line, Tumor, 616, Tuberculosis, Animals, Humans, Biomedical and Clinical Sciences, Macrophages, Mycobacterium tuberculosis, Toll-Like Receptor 2, Pleural Effusion, Mice, Inbred C57BL, Emerging Infectious Diseases, Good Health and Well Being, Biochemistry and Cell Biology, Proto-Oncogene Proteins c-akt
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