A mathematic model to reveal delicate cross-regulation between MAVS/STING, inflammasome and MyD88-dependent type I interferon signalling.

Early type I interferon is essential for antagonizing against malaria infection, which remains a significant global infectious disease. After Plasmodium yoelii YM infection, the activation of MAVS-, STING- and inflammasome-IRF3-mediated pathway could trigger the Socs1 expression to inhibit the TLR7-MyD88-IRF7-induced type I interferon production. However, the dynamic regulatory mechanisms of type I interferon response to YM infection and delicate cross-regulation of these signalling are far from clear. In current study, we established a mathematical model to systematically demonstrate that the MAVS-, STING- and inflammasome-mediated signalling pathways play distinct roles in regulating type I interferon response after YM infection; and the YM dose could significantly affect the difference of resistance to YM infection among MAVS, STING and inflammasome deficiency. Collectively, our study systematically elucidated the precise regulatory mechanisms of type I interferon signalling after YM infection and advanced the research on therapy of plasmodium infection by incorporating multiple signalling pathways at diverse time.