title: Mycobacterium tuberculosis PPE family protein Rv1808 manipulates cytokines profile via co-activation of MAPK and NF-κB signaling pathways.
abstract: OBJECTIVE
  Mycobacterium tuberculosis is an extremely successful intracellular pathogen armed with multiple tactics to subvert host immunity. PPE (Pro-Pro-Glu) family exclusively distributed in mycobacteria might be responsible for the virulence and pathogenicity of M.tuberculosis. The up-regulation of Rv1808 (PPE32) in many conditions prompted us to define its role in host innate immune response.
  
  
  METHODS
  The Rv1808 encoding gene was expressed in nonpathogenic fast growing Mycobacterium smegmatis, mycobacteria- Escherichia coli shuttle plasmid pNITmyc served as control. RT-PCR and ELISA were used to detect the transcription and translation of host cytokines in culture supernatant from macrophage incubated with purified Rv1808 protein. Pharmacological inhibitors were applied to confirm the specificity of the effector interfering of host signaling.
  
  
  RESULTS
  Recombinant Ms_Rv1808 survived better than Ms_pNITmyc within macrophage, accompanied by slightly higher host cell death. Rv1808 protein is associated with the cell wall and exposed on the cell surface. Physical binding of Rv1808 to TLR2 resulted in increase in the secretion of anti-inflammatory cytokine interleukin-10 (IL-10) and pro-inflammatory cytokines tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) possibly via co-activation of NF-κB and MAPK (p38MAPK, JNK and ERK) signalling.
  
  
  CONCLUSIONS
  Cell wall associated Rv1808 protein manipulated the host cytokines via MAPK and NF-κB signaling pathways.
authors: Institute of Modern Biopharmaceuticals, State Key Laboratory Breeding Base of Eco-Enviroment and Bio-Resource of the Three Gorges Area, Key Laboratory of Eco-environments in Three Gorges Reservoir Region, Ministry of Education, School of Life Sciences, Southwest University, Beibei, Chongqing, China.
authors: Wanyan
authors: W
authors: Deng
authors: Wu
authors: W
authors: Li
authors: Jie
authors: J
authors: Zeng
authors: Quanju
authors: Q
authors: Zhao
authors: Chunmei
authors: C
authors: Li
authors: Yuzhong
authors: Y
authors: Zhao
authors: Jianping
authors: J
authors: Xie
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D014376:Tuberculosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D020298:U937 Cells
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D016328:NF-kappa B; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D048049:Extracellular Signal-Regulated MAP Kinases