Toll-like receptor 4 confers inflammatory response to Suilysin.
Toll-like receptor 4 confers inflammatory response to Suilysin.
复制标题
Toll 样受体 4 赋予 Sulysin 炎症反应。
DOI：
10.3389/fmicb.2015.00644
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发表时间：
2015
影响因子：
5.2
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Bi L;Pian Y;Chen S;Ren Z;Liu P;Lv Q;Zheng Y;Zhang S;Hao H;Yuan Y;Jiang Y
猪链球菌2型（Streptococcussuisserotype 2，SS 2）是一种新发现的人类致病菌。2005年夏天在中国发生了一次大规模疫情。这次暴发的血清样本显示，链球菌中毒性休克样综合征（STSLS）患者的主要促炎细胞因子水平明显高于脑膜炎患者。然而，由SS 2引起的STSLS中的细胞因子风暴的潜在机制仍不清楚。在这项研究中，我们发现，猪溶血素（SLY）是SS 2的主要蛋白质炎症刺激和天然SLY（nSLY）刺激细胞因子独立于其溶血能力。有趣的是，少量的SLY（1000 Mol/L）诱导人PBMC长期释放TNF-α。我们还发现，nSLY刺激野生型巨噬细胞中的TNF-α，但不刺激携带TLR 4（P712 H）自发突变的小鼠巨噬细胞中的TNF-α。我们首次证明了SLY通过TLR 4刺激免疫细胞。此外，Myd 88 adaptor-p38-MAPK通路参与了这一过程。提示SLY诱导的TLR 4依赖性炎症反应可能参与了SS 2诱导的STSLS，p38-MAPK可作为靶点调控SS 2诱导的过量TNF-α释放。
Streptococcus suis serotype 2 (SS2) is an emerging human pathogen worldwide. A large outbreak occurred in the summer of 2005 in China. Serum samples from this outbreak revealed that levels of the main proinflammatory cytokines were significantly higher in patients with streptococcal toxic-shock-like syndrome (STSLS) than in patients with meningitis only. However, the mechanism underlying the cytokine storm in STSLS caused by SS2 remained unclear. In this study, we found that suilysin (SLY) is the main protein inflammatory stimulus of SS2 and that native SLY (nSLY) stimulated cytokines independently of its haemolytic ability. Interestingly, a small amount of SLY (Å Mol/L) induced strong, long-term TNF-α release from human PBMCs. We also found that nSLY stimulated TNF-α in wild-type macrophages but not in macrophages from mice that carried a spontaneous mutation in TLR4 (P712H). We demonstrated for the first time that SLY stimulates immune cells through TLR4. In addition, the Myd88 adaptor-p38-MAPK pathway was involved in this process. The present study suggested that the TLR4-dependent inflammatory responses induced by SLY in host might contribute to the STSLS caused by SS2 and that p38-MAPK could be used as a target to control the release of excess TNF-α induced by SS2.