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  • 标题:Toxoplasma gondii effector TgIST blocks type I interferon signaling to promote infection
  • 本地全文:下载
  • 作者:Sumit K. Matta ; Sumit K. Matta ; Philipp Olias
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2019
  • 卷号:116
  • 期号:35
  • 页码:17480-17491
  • DOI:10.1073/pnas.1904637116
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:In contrast to the importance of type II interferon-γ (IFN-γ) in control of toxoplasmosis, the role of type I IFN is less clear. We demonstrate here that TgIST, a secreted effector previously implicated in blocking type II IFN-γ signaling, also blocked IFN-β responses by inhibiting STAT1/STAT2-mediated transcription in infected cells. Consistent with a role for type I IFN in cell intrinsic control, ∆ Tgis t mutants were more susceptible to growth inhibition by murine and human macrophages activated with IFN-β. Additionally, type I IFN was important for production of IFN-γ by natural killer (NK) cells and recruitment of inflammatory monocytes at the site of infection. Mice lacking type I IFN receptors (Ifnar1 −/− ) showed increased mortality following infection with wild-type parasites and decreased virulence of ∆Tgist parasites was restored in Ifnar1 −/− mice. The findings highlight the importance of type I IFN in control of toxoplasmosis and illuminate a parasite mechanism to counteract the effects of both type I and II IFN-mediated host defenses..
  • 关键词:interferon ; central nervous system ; inflammatory monocyte ; NK cell ; transcriptome
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