Group A Streptococcus induces less p65 nuclear translocation and non-classical nuclear factor kappa B activation in macrophages, which possibly leads to a weaker inflammatory response
Group A Streptococcus induces less p65 nuclear translocation and non-classical nuclear factor kappa B activation in macrophages, which possibly leads to a weaker inflammatory response
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A 族链球菌在巨噬细胞中诱导较少的 p65 核转位和非经典核因子 kappa B 激活，这可能导致较弱的炎症反应
DOI：
10.1016/j.ijid.2016.01.018
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发表时间：
2016-03-01
影响因子：
8.4
通讯作者：
Wei，Lin
中科院分区：
文献类型：
--
作者：
Wu，Shuhui;Ma，Cuiqing;Wei，Lin
目的探讨A组链球菌（group A Streptococcus，GAS）感染巨噬细胞后的致病机制及GAS逃避免疫细胞吞噬的机制。结果GAS诱导的巨噬细胞炎症介质水平低于革兰氏阳性金黄色葡萄球菌和革兰氏阴性大肠杆菌。因此，研究了传统的炎症信号通路。发现GAS和S.金黄色葡萄球菌诱导Toll样受体（TLR）2和TLR 4表达，而革兰氏阴性E.大肠杆菌激活RAW264.7细胞TLR 4。虽然MyD 88，主要的衔接蛋白，被激活的三种病原体，有MyD 88在巨噬细胞中的表达没有差异。核因子-κ B（NF-κB）是经典的炎症信号转录因子。coli中，诱导的p65核转位较S弱。金黄色。有趣的是，GAS通过诱导p65-p52异源二聚体激活NF-κB，但不是经典的NF-κB异源二聚体（p65-p50），而E. coli通过诱导p65-p50和p65-p52异源二聚体激活NF-κB。aureusandE.大肠杆菌感染时，GAS诱导的巨噬细胞核转位较弱，NF-κB亚基结合较明显，可能导致炎症反应较弱。
ObjectivesThe aim of this study was to explore the pathogenic mechanism of group A Streptococcus (GAS) and to investigate how GAS evades phagocytosis by immune cells.MethodsThe classical inflammatory signaling pathway of macrophages infected with GAS was investigated by protein microarray, real-time PCR, Western blot, immunoprecipitation, and flow cytometry.ResultsGAS induced a lower level of inflammatory mediators in macrophages than either the Gram-positiveStaphylococcus aureusor the Gram-negativeEscherichia coli. Therefore, the conventional inflammatory signal pathway was investigated. It was found that GAS andS. aureusinduced both toll-like receptor (TLR)2 and TLR4 expression, while Gram-negativeE. colionly activated TLR4 in RAW264.7 cells. Although MyD88, the main adaptor protein, was activated by the three pathogens, there was no difference in MyD88 expression in macrophages. Nuclear factor kappa B (NF-κB) is the classical transcription factor of inflammatory signals, and the results of the present study showed that GAS, similar toE. coli, induced a weaker p65 nuclear translocation compared toS. aureus. Interestingly, GAS activated NF-κB by inducing p65–p52 heterodimer, but not the classical heterodimer of NF-κB (p65–p50), whileE. coliactivated NF-κB by inducing both p65–p50 and p65–p52 heterodimers.ConclusionsCompared toS. aureusandE. coliinfection, GAS induced a weaker nuclear translocation and distinct combination of NF-κB subunits in macrophages, which probably leads to a weak inflammatory response.