RRC ID 1180
Author Okuda J, Toyotome T, Kataoka N, Ohno M, Abe H, Shimura Y, Seyedarabi A, Pickersgill R, Sasakawa C.
Title Shigella effector IpaH9.8 binds to a splicing factor U2AF(35) to modulate host immune responses.
Journal Biochem. Biophys. Res. Commun.
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.
Volume 333(2)
Pages 531-9
Published 2005-7-29
DOI 10.1016/j.bbrc.2005.05.145
PII S0006-291X(05)01148-4
PMID 15950937
MeSH Animals Antigens, Bacterial / immunology* Antigens, Bacterial / metabolism* Bacterial Proteins / immunology* Bacterial Proteins / metabolism* Dysentery, Bacillary / immunology* Dysentery, Bacillary / metabolism* HeLa Cells Histocompatibility Antigens Class II / immunology Histocompatibility Antigens Class II / metabolism Humans Immunologic Factors / immunology Immunologic Factors / metabolism Lung / immunology* Lung / metabolism* Mice Mice, Inbred C57BL Nuclear Proteins / immunology* Nuclear Proteins / metabolism* RNA Splicing / immunology Ribonucleoproteins / immunology* Ribonucleoproteins / metabolism* Splicing Factor U2AF
IF 2.559
Times Cited 64
Pathogenic microorganisms ?