Short communicationTLR3 signaling is downregulated by a MAVS isoform in epithelial cells

- Extracellular poly(I:C) activates TLR3-dependent IFN-β expression in HCT116.
- MAVS silencing upregulates IFN-β production via upregulation of NF-κB and IRF3 signaling.
- TLR3 signaling is regulated by miniMAVS, a 50 kDa isoform of MAVS.

Innate immune responses to dsRNA result in signaling through the TLR3 pathway and/or the RIG-I/MDA-5/MAVS pathway which can activate type I IFN, proinflammatory cytokines and apoptosis. It is not clear whether MAVS could play a role in TLR3-dependent responses to extracellular dsRNA. Using a model of epithelial cells that express a functional TLR3 signaling pathway, we found that TLR3-dependent responses to extracellular dsRNA are negatively regulated by MAVS, precisely “miniMAVS”, a recently described 50 kDa isoform of MAVS. This regulation of TLR3 by a MAVS isoform constitutes an endogenous regulatory mechanism in epithelial cells that could help prevent a potentially damaging excessive inflammatory response.