Supeng Yin, Mengmeng Yuan, Sirui Zhang, Hongdan Chen, Jing Zhou, Tongyu He, Gang Li, Yanlan Yu, Fan Zhang, Ming Li, Yan Zhao
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引用次数: 0
摘要
在高致病性猪链球菌 2 株的致病过程中,枯草蛋白样蛋白酶-1(SspA-1)发挥了重要作用。然而,SspA-1 引发过度炎症反应的机制仍不清楚。在这项研究中,我们证明了 SspA-1 诱导的过度促炎细胞因子的产生需要 I 型 IFN 信号的激活。进一步的实验表明,TLR2 内体通路介导了 SspA-1 诱导的 I 型 IFN 信号转导和炎症反应。最后,我们绘制了相关通路的主要信号成分图,发现 TIR 适应蛋白 Mal、TRAM 和 MyD88 以及 IRF1 和 IRF7 的下游激活参与了这一通路。这些结果解释了SspA-1引发过度炎症反应的分子机制,并揭示了I型IFN在猪流感病毒2型感染中的新作用,可能为进一步了解猪流感病毒2型这一高致病性菌株的发病机制提供了线索。
Streptococcus suis Serotype 2 Type IV Secretion Effector SspA-1 Induces Proinflammatory Cytokine Production via TLR2 Endosomal and Type I Interferon Signaling.
The subtilisin-like protease-1 (SspA-1) plays an important role in the pathogenesis of a highly virulent strain of Streptococcus suis 2. However, the mechanism of SspA-1-triggered excessive inflammatory response is still unknown. In this study, we demonstrated that activation of type I IFN signaling is required for SspA-1-induced excessive proinflammatory cytokine production. Further experiments showed that the TLR2 endosomal pathway mediates SspA-1-induced type I IFN signaling and the inflammatory response. Finally, we mapped the major signaling components of the related pathway and found that the TIR adaptor proteins Mal, TRAM, and MyD88 and the downstream activation of IRF1 and IRF7 were involved in this pathway. These results explain the molecular mechanism by which SspA-1 triggers an excessive inflammatory response and reveal a novel effect of type I IFN in S. suis 2 infection, possibly providing further insights into the pathogenesis of this highly virulent S. suis 2 strain.
期刊介绍:
Published continuously since 1904, The Journal of Infectious Diseases (JID) is the premier global journal for original research on infectious diseases. The editors welcome Major Articles and Brief Reports describing research results on microbiology, immunology, epidemiology, and related disciplines, on the pathogenesis, diagnosis, and treatment of infectious diseases; on the microbes that cause them; and on disorders of host immune responses. JID is an official publication of the Infectious Diseases Society of America.