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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炎症小体激活负向调节 MyD88-IRF7 I 型 IFN 信号传导和抗疟疾免疫
DOI：
10.1038/s41467-018-07384-7
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发表时间：
2018-11-23
影响因子：
16.6
通讯作者：
Wang RF
中科院分区：
文献类型：
--
作者：
Yu X;Du Y;Cai C;Cai B;Zhu M;Xing C;Tan P;Lin M;Wu J;Li J;Wang M;Wang HY;Su XZ;Wang RF
炎性小体在炎症和针对病原体的免疫应答中起关键作用。然而，在疟疾感染的背景下，炎性小体激活是否或如何调节I型干扰素（IFN-I）信号传导仍然未知。在这里，我们表明，在炎症体传感器AIM 2，NLRP 3或衔接Caspase-1缺陷的小鼠产生高水平的IFN-I细胞因子，并对致命的约氏疟原虫YM感染有抵抗力。炎性小体信号转导的失活减少白细胞介素（IL）-1β的产生，但增加IFN-I的产生。从机制上讲，我们显示炎性小体激活增强IL-1β介导的MyD 88-TRAF 3-IRF 3信号传导和SOCS 1上调。然而，SOCS 1抑制MyD 88-IRF 7介导的IFN-I信号传导和浆细胞样树突状细胞中的细胞因子产生。相比之下，炎性小体组分的消融减少了SOCS 1诱导，并减轻了其对MyD 88-IRF 7-依赖性-IFN-I信号传导的抑制，导致高水平的IFN-α/β产生和宿主存活。我们的研究确定了一个以前未被认识到的作用，炎症小体激活的负调控IFN-I信号通路，并提供了潜在的目标，开发有效的疟疾疫苗。炎性小体是炎症过程和宿主对感染反应的重要组成部分。在这里，作者表明炎性小体激活调节MyD 88-IRF 7 I型IFN信号传导和抗疟疾免疫。
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 production. 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. The inflammasome is an essential component of inflammatory processes and the host response to infection. Here the authors show that inflammasome activation modulates MyD88-IRF7 type I IFN signalling and anti-malaria immunity.
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影响因子：
32.4
作者：
Sharma S;DeOliveira RB;Kalantari P;Parroche P;Goutagny N;Jiang Z;Chan J;Bartholomeu DC;Lauw F;Hall JP;Barber GN;Gazzinelli RT;Fitzgerald KA;Golenbock DT
通讯作者：
Golenbock DT
影响因子：
4.4
作者：
Bellocchio, S;Montagnoli, C;Romani, L
通讯作者：
Romani, L
影响因子：
3.1
作者：
Kordes, Maximilian;Matuschewski, Kai;Hafalla, Julius Clemence R.
通讯作者：
Hafalla, Julius Clemence R.
影响因子：
8.8
作者：
Kalantari P;DeOliveira RB;Chan J;Corbett Y;Rathinam V;Stutz A;Latz E;Gazzinelli RT;Golenbock DT;Fitzgerald KA
通讯作者：
Fitzgerald KA
I型干扰素信号在弗朗西斯拉感染过程中激活炎症体需要。
影响因子：
15.3
作者：
Henry, Thomas;Brotcke, Anna;Weiss, David S.;Thompson, Lucinda J.;Monack, Denise M.
通讯作者：
Monack, Denise M.