tailieunhanh - Báo cáo khoa học: The bacterium, nontypeable Haemophilus influenzae, enhances host antiviral response by inducing Toll-like receptor 7 expression

The incidence of mixed viral⁄bacterial infections has increased recently because of the dramatic increase in antibiotic-resistant strains, the emer-gence of new pathogens, and the resurgence of old ones. Despite the relat-ively well-known role of viruses in enhancing bacterial infections, the impact of bacterial infections on viral infections remains unknown. | ỊFEBS Journal The bacterium nontypeable Haemophilus influenzae enhances host antiviral response by inducing Toll-like receptor 7 expression Evidence for negative regulation of host antiviral response by CYLD Akihiro Sakai1 2 Tomoaki Koga1 Jae-Hyang Lim1 Hirofumi Jono1 Kazutsune Harada3 Erika Szymanski1 Haidong Xu1 Hirofumi Kai3 and Jian-Dong Li1 1 Department of Microbiology Immunology University of Rochester MedicalCenter NY USA 2 Gonda Department of Cell Molecular Biology House Ear Institute University of Southern California Los Angeles CA USA 3 Department of Molecular Medicine Kumamoto University Japan Keywords cylindromatosis mixed infection nontypeable Haemophilus influenzae signal transduction Toll-like receptor 7 Correspondence . Li Department of Microbiology Immunology Box 672 University of Rochester MedicalCenter 601 Elmwood Avenue Rochester NY 14642 USA Fax 1 585 276 2231 Tel 1 585 275 7195 E-mail Jian-Dong_Li@ These authors contributed equally to this work Received 12 March 2007 revised 23 May 2007 accepted 23 May 2007 doi The incidence of mixed viral bacterial infections has increased recently because of the dramatic increase in antibiotic-resistant strains the emergence of new pathogens and the resurgence of old ones. Despite the relatively well-known role of viruses in enhancing bacterial infections the impact of bacterial infections on viral infections remains unknown. In this study we provide direct evidence that nontypeable Haemophilus influenzae NTHi a major respiratory bacterial pathogen augments the host antiviral response by up-regulating epithelial Toll-like receptor 7 TLR7 expression in vitro and in vivo. Moreover NTHi induces TLR7 expression via a TLR2-MyD88-IRAK-TRAF6-IKK-NF-jB-dependent signaling pathway. Interestingly CYLD a novel deubiquitinase acts as a negative regulator of TLR7 induction by NTHi. Our study thus provides new insights into a novel role for bacterial infection in .

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