Shigella effector IpaH9.8 binds to a splicing factor U2AF(35) to modulate host immune responses |
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Authors: | Okuda Jun Toyotome Takahito Kataoka Naoyuki Ohno Mutsuhito Abe Hiroyuki Shimura Yoshiro Seyedarabi Arefeh Pickersgill Richard Sasakawa Chihiro |
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Institution: | Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8039, Japan. |
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Abstract: | 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, DeltaipaH9.8 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-1beta 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. |
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Keywords: | Shigella Anti-inflammatory effector IpaH9 8 U2AF35 Inhibition of splicing |
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