IL-1β promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation.
IL-1β promotes antimicrobial immunity in macrophages by regulating TNFR signaling and caspase-3 activation.
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DOI：
10.4049/jimmunol.1202688
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发表时间：
2013-04-15
期刊：
影响因子：
--
通讯作者：
Behar SM
中科院分区：
文献类型：
--
作者：
Jayaraman P;Sada-Ovalle I;Nishimura T;Anderson AC;Kuchroo VK;Remold HG;Behar SM
结核分枝杆菌（Mtb）的体内控制反映了宿主免疫和细菌逃避策略之间的平衡。通过剥夺细菌的细胞内生态位介导保护性免疫的效应TH1细胞被调节以防止过度炎症。一个关键的免疫调节分子是Tim3。虽然Tim3通常被认为下调TH1反应，但我们最近描述了它与Mtb感染巨噬细胞表达的Galectin-9的相互作用刺激IL-1β分泌，这是小鼠模型中生存所必需的。为什么IL-1β是宿主抵抗结核分枝杆菌感染所必需的尚不清楚。在这里，我们发现IL-1β通过募集其他抗菌效应分子直接杀死小鼠和人巨噬细胞中的Mtb。IL-1β通过上调TNF分泌和TNFR1细胞表面表达，直接增强巨噬细胞中TNF信号传导，并导致caspase-3的激活。因此，IL-1β和下游TNF的产生导致细胞内Mtb生长的caspase依赖性限制。
In vivo control of Mycobacterium tuberculosis (Mtb) reflects the balance between host-immunity and bacterial evasion strategies. Effector TH1 cells that mediate protective immunity by depriving the bacterium of its intracellular niche are regulated to prevent over exuberant inflammation. One key immunoregulatory molecule is Tim3. Although Tim3 is generally recognized to down regulate TH1 responses, we recently described that its interaction with Galectin-9 expressed by Mtb infected macrophages stimulates IL-1β secretion, which is essential for survival in the mouse model. Why IL-1β is required for host resistance to Mtb infection is unknown. Here we show that IL-1β directly kills Mtb in murine and human macrophages and does so through the recruitment of other antimicrobial effector molecules. IL-1β directly augments TNF signaling in macrophages through the upregulation of TNF secretion and TNFR1 cell surface expression, and results in activation of caspase-3. Thus, IL-1β and downstream TNF production leads to caspase-dependent restriction of intracellular Mtb growth.
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DOI：
10.1084/jem.20080767
发表时间：
2008-11-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen M;Divangahi M;Gan H;Shin DS;Hong S;Lee DM;Serhan CN;Behar SM;Remold HG
通讯作者：
Remold HG
影响因子：
3.2
作者：
Hunter, Robert L.;Jagannath, Chinnaswamy;Actor, Jeffrey K.
通讯作者：
Actor, Jeffrey K.
影响因子：
56.9
作者：
Kim, Bae-Hoon;Shenoy, Avinash R.;MacMicking, John D.
通讯作者：
MacMicking, John D.
影响因子：
30.5
作者：
Gan H;Lee J;Ren F;Chen M;Kornfeld H;Remold HG
通讯作者：
Remold HG
影响因子：
64.8
作者：
Monney, L;Sabatos, CA;Kuchroo, VK
通讯作者：
Kuchroo, VK