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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 J.-D. 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@urmc.rochester.edu These authors contributed equally to this work Received 12 March 2007 revised 23 May 2007 accepted 23 May 2007 doi 10.1111 j.1742-4658.2007.05899.x 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 .