Inflammasome activation negatively regulates MyD88-IRF7 type I IFN signaling and anti-malaria immunity

Xiao Yu, Yang Du, Chunmei Cai, Baowei Cai, Motao Zhu, Changsheng Xing, Peng Tan, Meng Lin, Jian Wu, Jian Li, Mingjun Wang, Helen Y. Wang, Xin-zhuan Su, Rong-Fu Wang

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

The inflammasome plays a critical role in inflammation and immune responses against pathogens. However, whether or how inflammasome activation regulates type I interferon (IFN-I) signaling in the context of malaria infection remain unknown. Here we show mice deficient in inflammasome sensors AIM2, NLRP3 or adaptor Caspase-1 produce high levels of IFN-I cytokines and are resistant to lethal Plasmodium yoelii YM infection. Inactivation of inflammasome signaling reduces interleukin (IL)-1β production, but increases IFN-I production. Mechanistically, we show inflammsome activation enhances IL-1β-mediated MyD88-TRAF3-IRF3 signaling and SOCS1 upregulation. However, SOCS1 inhibits MyD88-IRF7-mediated-IFN-I signaling and cytokine production in plasmacytoid dendritic cells. By contrast, ablation of inflammsome components reduces SOCS1 induction, and relieves its inhibition on MyD88-IRF7-dependent-IFN-I signaling, leading to high levels of IFN-α/β production and host survival. Our study identifies a previously unrecognized role of inflammasome activation in the negative regulation of IFN-I signaling pathways and provides potential targets for developing effective malaria vaccines.

Original languageEnglish (US)
Number of pages1
JournalNature Communications
Volume9
Issue number1
DOIs
StatePublished - Nov 23 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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