Inflammasome activation negatively regulates MyD88-IRF7 type I IFN signaling and anti-malaria immunity
Inflammasome activation negatively regulates MyD88-IRF7 type I IFN signaling and anti-malaria immunity
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DOI：
10.1038/s41467-018-07384-7
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发表时间：
2018
影响因子：
16.6
通讯作者：
Rong-fu Wang
中科院分区：
文献类型：
--
作者：
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
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 produc- tion. 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.
