title: Early secreted antigen ESAT-6 of Mycobacterium Tuberculosis promotes apoptosis of macrophages via targeting the microRNA155-SOCS1 interaction.
abstract: BACKGROUND
  The early secreted antigenic target 6-kDa protein (ESAT-6) of Mycobacterium tuberculosis (Mtb) not only acts as a key player for virulence but also exhibits a strong immunotherapeutic potential against Mtb. However, little is known about the molecular basis for its potential in immunotherapy. The present study was designed to unravel the role of miRNA-155 in ESAT-6-mediated enhancement of host immunity and apoptosis in macrophages.
  
  
  METHODS
  Lentivirus-mediated miR-155 sponge and miR-155 and SOCS1 overexpression vectors were developed in macrophages. TLR2- or p65-specific siRNA knockdown was employed to silence TLR2 or p65. Quantitative polymerase chain reaction and western blotting analyses were performed to determine mRNA and protein expression levels, respectively. Macrophage apoptosis was analyzed by flow cytometry.
  
  
  RESULTS
  ESAT-6 significantly increased miR-155 expression, which was dependent on TLR2/NF-κB activation in macrophages. Induced expression of miRNA-155 was required for the ESAT-6-mediated protective immune response and macrophage apoptosis. ESAT-6 promoted macrophage apoptosis by targeting the miR-155-SOCS1 pathway. The differential expression levels of TLR2, BIC, and SOCS1 were involved in regulating the immune response in human peripheral blood mononuclear cells of patients with active tuberculosis (TB) and latent TB (LTB).
  
  
  CONCLUSIONS
  ESAT-6 promotes apoptosis of macrophages via targeting the miRNA155-SOCS1 interaction.
authors.affiliation: Department of Clinical Laboratory, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Shaojun
authors.initials: S
authors.lastname: Yang
authors.forename: Fake
authors.initials: F
authors.lastname: Li
authors.forename: Shuangrong
authors.initials: S
authors.lastname: Jia
authors.forename: Kejun
authors.initials: K
authors.lastname: Zhang
authors.forename: Wenbing
authors.initials: W
authors.lastname: Jiang
authors.forename: Ya
authors.initials: Y
authors.lastname: Shang
authors.forename: Kai
authors.initials: K
authors.lastname: Chang
authors.forename: Shaoli
authors.initials: S
authors.lastname: Deng
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D009169:Mycobacterium tuberculosis / Q000378:metabolism*; D034622:RNA Interference; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014376:Tuberculosis / Q000378:metabolism / Q000473:pathology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; C525005:ESAT-6 antigen, Mycobacterium leprae; D015850:Interleukin-6; D035683:MicroRNAs; D011994:Recombinant Proteins; D050826:Suppressor of Cytokine Signaling Proteins; D051195:Toll-Like Receptor 2; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha