title: Unphosphorylated STAT1 represses apoptosis in macrophages duringMycobacteriumtuberculosisinfection.
abstract: In murine macrophages infected withMycobacterium tuberculosis(Mtb), the level of phosphorylated STAT1 (P-STAT1), which drives the expression of many pro-apoptosis genes, increases quickly but then declines over a period of hours. By contrast, infection induces a continued increase in the level of unphosphorylated STAT1 that persists for several days. Here, we found that the level of unphosphorylated STAT1 correlated with the intracellular bacterial burden during the later stages of infection. To investigate the significance of a high level of unphosphorylated STAT1, we increased its concentration exogenously, and found that the apoptosis rate induced byMtbwas sufficiently decreased. Further experiments confirmed that unphosphorylated STAT1 affects the expression of several immune-associated genes and lessens the sensitivity of macrophages to CD95 (FAS)-mediated apoptosis duringMtbinfection. Furthermore, we characterized 149 proteins that interacted with unphosphorylated STAT1 and the interactome network. The cooperation between unphosphorylated STAT1 and STAT3 results in downregulation of CD95 expression. Additionally, we verified that unphosphorylated STAT1 and IFIT1 competed for binding to eEF1A. Taken together, our data show that the role of unphosphorylated STAT1 differs from that of P-STAT1, and represses apoptosis in macrophages to promote immune evasion duringMtbinfection.
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Kezhen
authors.initials: K
authors.lastname: Yao
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Yongyan
authors.initials: Y
authors.lastname: Wu
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Fayang
authors.initials: F
authors.lastname: Liu
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Northwest A&F University, Yangling 712100, Shaanxi, China zhy1956@263.net.|Key Laboratory of Animal Biotechnology, Ministry of Agriculture, Northwest A&F University, Yangling 712100, Shaanxi, China.
authors.forename: Yong
authors.identifier: 0000-0001-9811-3019
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000378:metabolism; D053222:Fas Ligand Protein / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism* / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D020648:Peptide Elongation Factor 1 / Q000378:metabolism; D010766:Phosphorylation; D060066:Protein Interaction Maps; D000067996:RAW 264.7 Cells; D016601:RNA-Binding Proteins; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D014158:Transcription, Genetic; D014376:Tuberculosis / Q000378:metabolism / Q000382:microbiology; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D053222:Fas Ligand Protein; C092573:Ifit1 protein, mouse; D020648:Peptide Elongation Factor 1; D016601:RNA-Binding Proteins; D050794:STAT1 Transcription Factor; D050796:STAT3 Transcription Factor; C000606749:eEF1A-1 protein, mouse; D019014:fas Receptor
keywords: Cell apoptosis; Immune evasion; Mycobacterium tuberculosis; Protein interactome; STAT1