Co-ordinated Role of TLR3, RIG-I and MDA5 in the Innate Response to Rhinovirus in Bronchial Epithelium

PLoS Pathogens

Ross P. Walton¹  Deborah L. Clarke¹  Michael R. Edwards¹  Jennifer J. Haas¹  Annemarie Sykes²  Onn M. Kon²  Jie Zhu²  Peter K. Jeffery²  Louise Slater²  Takashi Fujita³  Maria G. Belvisi⁴  Nathan W. Bartlett⁵  Sebastian L. Johnston⁵  Simon D. Message⁵  Samer Dahdaleh⁵ 

[1] Centre for Respiratory Infection, London, United Kingdom;Department of Respiratory Medicine, National Heart & Lung Institute, Imperial College London, London, United Kingdom;Imperial Healthcare NHS Trust, London, United Kingdom;Lung Pathology, National Heart & Lung Institute, Imperial College London, London, United Kingdom;MRC & Asthma UK Centre in Allergic Mechanisms of Asthma, London, United Kingdom

关键词: Small interfering RNAs;    RNA helicases;    Gene expression;    Cytokines;    Interferons;    Toll-like receptors;    Immune receptor signaling;    Mouse models;   

DOI  :  10.1371/journal.ppat.1001178

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY