Shigella effector IpaH9.8 binds to a splicing factor U2AF35 to modulate host immune responses
Shigella effector IpaH9.8 binds to a splicing factor U2AF35 to modulate host immune responses
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DOI：
10.1016/j.bbrc.2005.05.145
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发表时间：
2005-07-29
影响因子：
3.1
通讯作者：
Sasakawa, C
中科院分区：
文献类型：
--
作者：
Okuda, J;Toyotome, T;Sasakawa, C
通过III型分泌系统注射到宿主细胞中的志贺氏菌效应子参与感染的各个方面。在这里，我们表明，效应之一，IpaH9.8，在调节志贺氏菌感染的炎症反应中发挥作用。在小鼠肺部感染模型中，Delta ipaH9.8突变体引起更严重的炎症反应，促炎细胞因子产生水平比野生型志贺氏菌增加，导致细菌定植减少30倍。结合试验表明，IpaH 9.8对U2 AF（35）具有特异性亲和力，U2 AF（35）是一种哺乳动物剪接因子，可干扰U2 AF（35）依赖性剪接（如IgM前体mRNA测定）。通过RT-PCR检测，降低HeLa细胞中的U2 AF（35）水平和用野生型感染HeLa细胞引起il-8、RANTES、GM-CSF和il-1 β基因表达的降低。结果表明，IpaH9.8在志贺氏菌感染中发挥作用，以优化宿主炎症反应，从而促进宿主上皮细胞内的细菌定植。(c)2005年爱思唯尔公司All rights reserved.
Shigella effectors injected into the host cell via the type III secretion system are involved in various aspects of infection. Here, we show that one of the effectors, IpaH9.8, plays a role in modulating inflammatory responses to Shigella infection. In murine lung infection model, Delta ipaH9.8 mutant caused more severe inflammatory responses with increased pro-inflammatory cytokine production levels than did wild-type Shigella, which resulted in a 30-fold decrease in bacterial colonization. Binding assays revealed that IpaH9.8 has a specific affinity to U2AF(35), a mammalian splicing factor, which interferes with U2AF(35)-dependent splicing as assayed for IgM pre-mRNA. Reducing the U2AF(35) level in HeLa cells and infecting HeLa cells with wild-type caused a decrease in the expression of the il-8, RANTES, GM-CSF, and il-1 beta genes as examined by RT-PCR. The results indicate that IpaH9.8 plays a role in Shigella infection to optimize the host inflammatory responses, thus facilitating bacterial colonization within the host epithelial cells. (c) 2005 Elsevier Inc. All rights reserved.