A mathematic model to reveal delicate cross-regulation between MAVS/STING, inflammasome and MyD88-dependent type I interferon signalling.
A mathematic model to reveal delicate cross-regulation between MAVS/STING, inflammasome and MyD88-dependent type I interferon signalling.
复制标题
揭示 MAVS/STING、炎性体和 MyD88 依赖性 I 型干扰素信号传导之间微妙交叉调节的数学模型
DOI：
10.1111/jcmm.15768
复制
发表时间：
2020-10
影响因子：
5.3
通讯作者：
Yu X
中科院分区：
文献类型：
--
作者：
Cai C;Yu X
早期I型干扰素对于对抗疟疾感染至关重要，疟疾仍然是一种重要的全球传染病。约氏疟原虫 YM 感染后，MAVS、STING 和炎症小体 IRF3 介导的通路激活可触发 Socs1 表达，抑制 TLR7-MyD88-IRF7 诱导的 I 型干扰素产生。然而，I 型干扰素对 YM 感染反应的动态调节机制以及这些信号传导的微妙交叉调节尚不清楚。在本研究中，我们建立了一个数学模型来系统地证明MAVS、STING和炎性体介导的信号通路在调节YM感染后I型干扰素反应中发挥着不同的作用。 YM剂量可显着影响MAVS、STING和炎性体缺乏者对YM感染抵抗力的差异。总的来说，我们的研究系统地阐明了YM感染后I型干扰素信号传导的精确调节机制，并通过在不同时间整合多种信号传导途径推进了疟原虫感染治疗的研究。
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.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
29.7
作者：
Brubaker SW;Bonham KS;Zanoni I;Kagan JC
通讯作者：
Kagan JC
影响因子：
32.4
作者：
Paludan SR;Bowie AG
通讯作者：
Bowie AG
影响因子：
30.3
作者：
Coban, Cevayir;Igari, Yoshikatsu;Akira, Shizuo
通讯作者：
Akira, Shizuo
影响因子：
11.8
作者：
Ouattara, Amed;Laurens, Matthew B.
通讯作者：
Laurens, Matthew B.