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 Sakai, Tomoaki Koga, Jae Hyang Lim, Hirofumi Jono, Kazutsune Harada, Erika Szymanski, Haidong Xu, Hirofumi Kai, Jian Dong Li

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

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- κB-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 enhancing host antiviral response and further identifies CYLD for the first time as a critical negative regulator of host antiviral response.

Original languageEnglish
Pages (from-to)3655-3668
Number of pages14
JournalFEBS Journal
Volume274
Issue number14
DOIs
StatePublished - Jul 2007

Keywords

  • Cylindromatosis
  • Mixed infection
  • Nontypeable Haemophilus influenzae
  • Signal transduction
  • Toll-like receptor 7

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