アクティブボード・２００８年１０月
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研究発表を行った学会；
・Gordon Research Conference-Acute Respiratory Infection.
　２００８年　３月１１日(Ventura, CA, USA)

タイトル；Tumor Suppressor Cylindromatosis (CYLD) Acts as a Negative Regulator for nontypeable Haemophilus influenzae-induced Toll-like receptor 7 expression in epithelial cells.
　
発表者；　古賀　友紹　氏
　　　（熊本大学　大学院薬学教育部　遺伝子機能応用学分野）
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 virus in enhancing bacterial infections, the impact of bacterial infections on viral infections remains unknown.
In the present study, we provide direct evidence that Gram-negative bacterium nontypeable Haemophilus influenzae (NTHi), a major respiratory bacterial pathogen, augments the host antiviral response by up-regulating toll-like receptor (TLR) 7 expression in human lung epithelial A549 cells in vitro and in the lungs of C57BL/6 mice in vivo. Moreover, NTHi-induced TLR7 expression is regulated by the activation of TLR2 and the downstream signaling pathway including MyD88-IRAK1-TRAF6-IKKbeta-NF-kappaB signaling pathway in vitro. The requirement of TLR2 for NTHi-induced TLR7 expression is confirmed by using lungs from TLR2 knockout mice. Interestingly, a deubiquitinating enzyme CYLD, loss of which causes benign human tumor cylindromatosis, acts as a negative regulator of NTHi-induced TLR7 expression in vitro and in lungs of CYLD knockout mice in vivo. Furthermore, we demonstrate that NTHi strongly induces CYLD expression in vitro and in vivo, thereby suggesting that NTHi-induced TLR7 up-regulation is negatively regulated by CYLD in an autoregulatory feedback manner. Because the morbidity of mixed viral/bacterial infections has increased, our study provides new insights into a novel role of bacterial infection on viral infections.