title: Shigella effector IpaH9.8 binds to a splicing factor U2AF(35) to modulate host immune responses.
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.
authors.affiliation: Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8039, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Okuda
authors.forename: Takahito
authors.initials: T
authors.lastname: Toyotome
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Kataoka
authors.forename: Mutsuhito
authors.initials: M
authors.lastname: Ohno
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Abe
authors.forename: Yoshiro
authors.initials: Y
authors.lastname: Shimura
authors.forename: Arefeh
authors.initials: A
authors.lastname: Seyedarabi
authors.forename: Richard
authors.initials: R
authors.lastname: Pickersgill
authors.forename: Chihiro
authors.initials: C
authors.lastname: Sasakawa
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000378:metabolism*; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism*; D004405:Dysentery, Bacillary / Q000276:immunology* / Q000378:metabolism*; D006367:HeLa Cells; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000276:immunology* / Q000378:metabolism*; D012326:RNA Splicing / Q000276:immunology; D012261:Ribonucleoproteins / Q000276:immunology* / Q000378:metabolism*; D000072668:Splicing Factor U2AF
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D000949:Histocompatibility Antigens Class II; D007155:Immunologic Factors; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C076753:U2AF1 protein, human; C063500:ipaH protein, Shigella flexneri