PLoS Pathogens (Nov 2010)

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

  • Louise Slater,
  • Nathan W Bartlett,
  • Jennifer J Haas,
  • Jie Zhu,
  • Simon D Message,
  • Ross P Walton,
  • Annemarie Sykes,
  • Samer Dahdaleh,
  • Deborah L Clarke,
  • Maria G Belvisi,
  • Onn M Kon,
  • Takashi Fujita,
  • Peter K Jeffery,
  • Sebastian L Johnston,
  • Michael R Edwards

DOI
https://doi.org/10.1371/journal.ppat.1001178
Journal volume & issue
Vol. 6, no. 11
p. e1001178

Abstract

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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.