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A MyD88–JAK1–STAT1 complex directly induces SOCS-1 expression in macrophages infected with Group A Streptococcus

Cellular & Molecular Immunology volume 12, pages 373–383 (2015)Cite this article

Abstract

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-β 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-β 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-β 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.

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Author notes

  1. Dr L Wei, Hebei Medical University, Shijiazhuang 050017, China. E-mail: weilin21@sina.com

Authors and Affiliations

  1. Hebei Medical University, Shijiazhuang, China

    Jinghua Wu, Cuiqing Ma, Shuhui Wu, Gao Xue, Xinli Shi, Zhang Song & Lin Wei

  2. Hebei United University Affiliated Hospital, Tangshan, China

    Jinghua Wu

  3. Tangshan City Hospital of Traditional Chinese Medicine, Tangshan, China

    Haixin Wang

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Wu, J., Ma, C., Wang, H. et al. A MyD88–JAK1–STAT1 complex directly induces SOCS-1 expression in macrophages infected with Group A Streptococcus. Cell Mol Immunol 12, 373–383 (2015). https://doi.org/10.1038/cmi.2014.107

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