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

Abstract

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.

Identification and functional characterizations of a novel TRIF gene from grass carp (Ctenopharyngodon idella)

“…Inhibition of TLR3 and TRIF using siRNA reduces rhinovirus induced RIG-I/MDA5 (Slater et al, 2010). Over-expression of TRIF in primary human bronchial epithelial cells significantly up-regulates mRNA expressions of RIG-I and MDA5 (two members of RLRs) (Slater et al, 2010). This is the first report that TRIF regulates RIG-I in fishes.…”

“…In mouse, RIG-I/MDA5 and the TLR3/TRIF signaling axes cooperate for efficient innate antiviral immune responses (Negishi et al, 2008). Antiviral defense within bronchial epithelium requires co-ordinated recognition of rhinovirus infection, initially via TLR3/TRIF and later via inducible RIG-I and MDA5 (Slater et al, 2010). Inhibition of TLR3 and TRIF using siRNA reduces rhinovirus induced RIG-I/MDA5 (Slater et al, 2010).…”

“…Antiviral defense within bronchial epithelium requires co-ordinated recognition of rhinovirus infection, initially via TLR3/TRIF and later via inducible RIG-I and MDA5 (Slater et al, 2010). Inhibition of TLR3 and TRIF using siRNA reduces rhinovirus induced RIG-I/MDA5 (Slater et al, 2010). Over-expression of TRIF in primary human bronchial epithelial cells significantly up-regulates mRNA expressions of RIG-I and MDA5 (two members of RLRs) (Slater et al, 2010).…”

Staphylococcus aureus colonization and non-influenza respiratory viruses: Interactions and synergism mechanisms

“…The innate immune system recognizes rhinovirus by different Pattern Recognition Receptors (PRRs) including membrane and endosomal Toll-like Receptors (TLRs) and cytoplasmic inducible RNA helicases like retinoic acid-inducible gene-1 (RIG-I) or melanoma differentiation-associated protein 5 (MDA5) [48]. Rhinovirus infection promotes pro-inflammatory cytokines and IFN production mainly through the activation of NFκB [49,50]. …”

Retinoic acid-inducible gene-I-like receptor (RLR)-mediated antiviral innate immune responses in the lower respiratory tract: Roles of TRAF3 and TRAF5

“…BECs recognize dsRNA via TLR3 and RLRs [29,30]. Accordingly, antiviral defense in the bronchial epithelium requires the coordinated recognition of rhinovirus infection, which initially occurs via TLR3 and later involves RIG-I and MDA5 [29].…”