| First Author | Yu X | Year | 2018 |
| Journal | Nat Commun | Volume | 9 |
| Issue | 1 | Pages | 4964 |
| PubMed ID | 30470758 | Mgi Jnum | J:269156 |
| Mgi Id | MGI:6268208 | Doi | 10.1038/s41467-018-07384-7 |
| Citation | Yu X, et al. (2018) Inflammasome activation negatively regulates MyD88-IRF7 type I IFN signaling and anti-malaria immunity. Nat Commun 9(1):4964 |
| abstractText | 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)-1beta production, but increases IFN-I production. Mechanistically, we show inflammsome activation enhances IL-1beta-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-alpha/beta 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. |
