Inflammasome Activation Dampens Type I IFN Signaling to Strengthen Anti- <i>Toxoplasma</i> Immunity
Zhiqiang Hu, Dan Wu, Jiansen Lu, Yufen Zhang, Shao-Meng Yu, Yingchao Xie, Hongyu Li, Jianwu Yang, De‐Hua Lai, Ke Zeng, Huaji Jiang, Zhao‐Rong Lun, Xiao Yu
Abstract
As a key component of innate immunity, inflammasome is critical for host antitoxoplasmosis immunity, but the underlying mechanisms are still elusive. In this study, we found that inflammasome signaling was activated by PAMPs of T. gondii, which generated a protective immunity against T. gondii invasion by suppressing type I interferon (IFN-I) production. Mechanically, inflammasome-coupled IL-1β signaling triggered the expression of negative regulator SOCS1, which bound to IRF3 to inhibit IFN-I production. The role of IFN-I in anti-T. gondii immunity is little studied and controversial, and here we also found IFN-I is harmful to host antitoxoplasmosis immunity by using knockout mice and recombinant proteins. In general, our study identifies a protective role of inflammasomes to the host during T. gondii infection and a novel mechanism by which inflammasome suppresses IFN-I signaling in antitoxoplasmosis immunity, which will likely provide new insights into therapeutic targets for toxoplasmosis and highlight the cross talk between innate immune signaling in infectious diseases prevention.