Co-ordinated role of TLR3,RIG-I and MDA5 in the innate response to rhinovirus in bronchial epithelium

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. © 2010 slater et al.