title: Induction of CCL8/MCP-2 by mycobacteria through the activation of TLR2/PI3K/Akt signaling pathway.
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.
authors: Shanghai TB Key Laboratory, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Haipeng
authors: H
authors: Liu
authors: Zhonghua
authors: Z
authors: Liu
authors: Jianxia
authors: J
authors: Chen
authors: Ling
authors: L
authors: Chen
authors: Xin
authors: X
authors: He
authors: Ruijuan
authors: R
authors: Zheng
authors: Hong
authors: H
authors: Yang
authors: Peng
authors: P
authors: Song
authors: Dong
authors: D
authors: Weng
authors: Haili
authors: H
authors: Hu
authors: Lin
authors: L
authors: Fan
authors: Heping
authors: H
authors: Xiao
authors: Stefan H E
authors: SH
authors: Kaufmann
authors: Joel
authors: J
authors: Ernst
authors: Baoxue
authors: B
authors: Ge
mesh_terms: D000328:Adult; D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D054412:Chemokine CCL8 / Q000235:genetics / Q000378:metabolism*; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D015151:Immunoblotting; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008875:Middle Aged; D009163:Mycobacterium bovis / Q000502:physiology; D009169:Mycobacterium tuberculosis / Q000502:physiology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010996:Pleural Effusion / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism*; D014396:Tuberculosis, Pleural / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism
chemical_list: D054412:Chemokine CCL8; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D051195:Toll-Like Receptor 2