A MyD88-JAK1-STAT1 complex directly induces SOCS-1 expression in macrophages infected with Group A Streptococcus
A MyD88-JAK1-STAT1 complex directly induces SOCS-1 expression in macrophages infected with Group A Streptococcus
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DOI：
10.1038/cmi.2014.107
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发表时间：
2015-05-01
影响因子：
24.1
通讯作者：
Wei, Lin
中科院分区：
文献类型：
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作者：
Wu, Jinghua;Ma, Cuiqing;Wei, Lin
一些病原体可以利用宿主细胞因子信号传导抑制因子1 （host suppressor of cytokine signaling, SOCS-1）这一重要的负反馈分子作为免疫逃避的主要方式。本研究发现，A组链球菌（GAS）能够诱导RAW264.7和BMDM巨噬细胞中SOCS-1的表达。ifn - β通过GAS诱导细胞因子表达，在巨噬细胞中参与GAS诱导的SOCS-1表达，是SOCS-1表达的经典途径。然而，在本研究中，当GAS感染的细胞与抗ifn - β单克隆抗体孵育时，GAS也诱导STAT1激活和SOCS-1表达。此外，通过将TLR4(-/-) BMDM巨噬细胞与野生型（WT）细胞进行比较，我们发现TLR4在SOCS-1的诱导中也起着重要作用。MyD88是TLR4的接头蛋白，在巨噬细胞中通过与Janus kinase 1 （JAK1）和信号转导及转录激活因子1 （STAT1）形成复合物，参与STAT1的激活和磷酸化。在MyD88（-/-）巨噬细胞中，气体刺激的STAT1表达严重受损，而JAK1的表达未受影响，这表明MyD88参与了STAT1的表达和磷酸化。综上所述，这些数据表明，除了ifn - β信号和MyD88复合物的形成外，JAK1和STAT1还通过一种新的途径直接诱导gas感染巨噬细胞中SOCS-1的表达，这可能更有利于快速的细菌感染。
Some pathogens can use host suppressor of cytokine signaling 1 (SOCS-1), an important negative-feedback molecule, as the main mode of immune evasion. Here we found that group A Streptococcus (GAS) is capable of inducing SOCS-1 expression in RAW264.7 and BMDM macrophages. IFN-beta plays a role in GAS-induced SOCS-1 expression in macrophages following the induction of cytokine expression by GAS, representing the classical pathway of SOCS-1 expression. However, GAS also induced STAT1 activation and SOCS-1 expression when GAS-infected cells were incubated with anti-IFN-beta monoclonal antibody in this study. Moreover, upon comparing TLR4(-/-) BMDM macrophages with wild-type (WT) cells, we found that TLR4 also plays an essential role in the induction of SOCS-1. MyD88, which is an adaptor protein for TLR4, contributes to STAT1 activation and phosphorylation by forming a complex with Janus kinase 1 (JAK1) and signal transducer and activator of transcription 1 (STAT1) in macrophages. GAS-stimulated expression of STAT1 was severely impaired in MyD88(-/-) macrophages, whereas expression of JAK1 was unaffected, suggesting that MyD88 was involved in STAT1 expression and phosphorylation. Together, these data demonstrated that in addition to IFN-beta signaling and MyD88 complex formation, JAK1 and STAT1 act in a novel pathway to directly induce SOCS-1 expression in GAS-infected macrophages, which may be more conducive to rapid bacterial infection.