title: Endoplasmic reticulum stress pathway-mediated apoptosis in macrophages contributes to the survival of Mycobacterium tuberculosis.
abstract: BACKGROUND
  Apoptosis is thought to play a role in host defenses against intracellular pathogens, including Mycobacterium tuberculosis (Mtb), by preventing the release of intracellular components and the spread of mycobacterial infection. This study aims to investigate the role of endoplasmic reticulum (ER) stress mediated apoptosis in mycobacteria infected macrophages.
  
  
  RESULTS
  Here, we demonstrate that ER stress-induced apoptosis is associated with Mtb H37Rv-induced cell death of Raw264.7 murine macrophages. We have shown that Mtb H37Rv induced apoptosis are involved in activation of caspase-12, which resides on the cytoplasmic district of the ER. Mtb infection increase levels of other ER stress indicators in a time-dependent manner. Phosphorylation of eIF2α was decreased gradually after Mtb H37Rv infection signifying that Mtb H37Rv infection may affect eIF2α phosphorylation in an attempt to survive within macrophages. Interestingly, the survival of mycobacteria in macrophages was enhanced by silencing CHOP expression. In contrast, survival rate of mycobacteria was reduced by phosphorylation of the eIF2α. Futhermore, the levels of ROS, NO or CHOP expression were significantly increased by live Mtb H37Rv compared to heat-killed Mtb H37Rv indicating that live Mtb H37Rv could induce ER stress response.
  
  
  CONCLUSIONS
  These findings indicate that eIF2α/CHOP pathway may influence intracellular survival of Mtb H37Rv in macrophages and only live Mtb H37Rv can induce ER stress response. The data support the ER stress pathway plays an important role in the pathogenesis and persistence of mycobacteria.
authors.affiliation: Department of Microbiology, College of Medicine, Chungnam National University, Daejeon, South Korea.
authors.forename: Yun-Ji
authors.initials: YJ
authors.lastname: Lim
authors.forename: Ji-Ae
authors.initials: JA
authors.lastname: Choi
authors.forename: Hong-Hee
authors.initials: HH
authors.lastname: Choi
authors.forename: Soo-Na
authors.initials: SN
authors.lastname: Cho
authors.forename: Hwa-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Eun-Kyeong
authors.initials: EK
authors.lastname: Jo
authors.forename: Jeong-Kyu
authors.initials: JK
authors.lastname: Park
authors.forename: Chang-Hwa
authors.initials: CH
authors.lastname: Song
mesh_terms: D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism / Q000382:microbiology; D059865:Endoplasmic Reticulum Stress / Q000235:genetics; D004789:Enzyme Activation; D020717:Eukaryotic Initiation Factor-2B / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism / Q000382:microbiology; D008264:Macrophages / Q000166:cytology* / Q000201:enzymology / Q000382:microbiology*; D053858:Metabolic Networks and Pathways; D051379:Mice; D050296:Microbial Viability; D009169:Mycobacterium tuberculosis / Q000166:cytology* / Q000502:physiology; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D014376:Tuberculosis / Q000382:microbiology / Q000473:pathology
chemical_list: D015415:Biomarkers; D020717:Eukaryotic Initiation Factor-2B; D012333:RNA, Messenger; D051742:Transcription Factor CHOP; D020169:Caspases