| Title | Co-ordinated role of TLR3, RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium. | ||
| Author | Slater, Louise; Bartlett, Nathan W; Haas, Jennifer J; Zhu, Jie; Message, Simon D; Walton, Ross P; Sykes, Annemarie; Dahdaleh, Samer; Clarke, Deborah L; Belvisi, Maria G; Kon, Onn M; Fujita, Takashi; Jeffery, Peter K; Johnston, Sebastian L; Edwards, Michael R | ||
| Journal | PLoS Pathog | Publication Year/Month | 2010-Nov |
| PMID | 21079690 | PMCID | PMC2973831 |
| Affiliation | 1.Department of Respiratory Medicine, National Heart & Lung Institute, Imperial College London, London, United Kingdom. | ||
The relative roles of the endosomal TLR3/7/8 versus the intracellular RNA helicases RIG-I and MDA5 in viral infection is much debated. We investigated the roles of each pattern recognition receptor in rhinovirus infection using primary bronchial epithelial cells. TLR3 was constitutively expressed; however, RIG-I and MDA5 were inducible by 8-12 h following rhinovirus infection. Bronchial epithelial tissue from normal volunteers challenged with rhinovirus in vivo exhibited low levels of RIG-I and MDA5 that were increased at day 4 post infection. Inhibition of TLR3, RIG-I and MDA5 by siRNA reduced innate cytokine mRNA, and increased rhinovirus replication. Inhibition of TLR3 and TRIF using siRNA reduced rhinovirus induced RNA helicases. Furthermore, IFNAR1 deficient mice exhibited RIG-I and MDA5 induction early during RV1B infection in an interferon independent manner. Hence anti-viral defense within bronchial epithelium requires co-ordinated recognition of rhinovirus infection, initially via TLR3/TRIF and later via inducible RNA helicases.