Mycobacterium tuberculosis PE13 (Rv1195) manipulates the host cell fate via p38-ERK-NF-κB axis and apoptosis

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• 作者：Hui Li ; Qiming Li ; Zhaoxiao Yu ; Mingliang Zhou ; Jianping Xie
• 刊名：Apoptosis
• 出版年：2016
• 出版时间：July 2016
• 年：2016
• 卷：21
• 期：7
• 页码：795-808
• 全文大小：4,645 KB
• 刊物类别：Medicine
• 刊物主题：Medicine & Public Health
  Oncology
  Cancer Research
  Cell Biology
  Biochemistry
  Virology
  
• 出版者：Springer Netherlands
• ISSN：1573-675X
• 卷排序：21

文摘

PE/PPE family proteins are mycobacteria unique molecules, named after their N-terminal conserved PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains. Mycobacterium tuberculosis (Mtb) PE family gene encoded cell surface proteins are previously reported to be involved in virulence and interaction with host. To explore the role of a novel PE member (PE13, Rv1195), M. smegmatis was used as surrogate host. The study showed that Rv1195 was a cell wall associated protein. Rv1195 can enhance the survival of recombinants under stress conditions such as H₂O₂, SDS, low pH. This is largely due to the upregulated transcription of Rv1195, since diverse stresses can increase the promoter activity of Rv1195 gene, consistent with enhanced survival within macrophages. Ms_Rv1195 infection also increased the production of interlukin-6 (IL-6) and IL-1β from macrophages, while decreased the secretion of suppressor of cytokine signaling 3 (SOCS3) in comparison with the vector-only control. The cell death was also precipitated by the Ms_Rv1195 infection. Inhibitors treatment showed that the p38-ERK-NF-κB axis was involved in the Rv1195 triggered change of IL-6 and IL-1β expression. In summary, we showed that PE13 (Rv1195) is a new PE family member actively engaged in the interaction between Mycobacterium and host, signaling through p38-ERK-NF-κB axis and apoptosis.KeywordsMycobacterium tuberculosisPE13MacrophageIL-6IL-1βSuppressor of cytokine signaling 3Apoptosis