Cigarette Smoke Dampens Anti-viral Signaling in Small Airway Epithelial Cells by Disrupting TLR3 Cleavage.

Cigarette Smoke Dampens Anti-viral Signaling in Small Airway Epithelial Cells by Disrupting TLR3 Cleavage.

Am J Physiol Lung Cell Mol Physiol. 2017 Dec 14;:

Authors: Duffney PF, McCarthy CE, Nogales A, Thatcher TH, Martinez-Sobrido L, Phipps RP, Sime PJ

Abstract
Cigarette smokers and people exposed to secondhand smoke are at an increased risk for pulmonary viral infections, yet the mechanism responsible for this heightened susceptibility is not understood. To understand the effect of cigarette smoke on susceptibility to viral infection we used an air-liquid interface culture system, and exposed primary human small airway epithelial cells (SAEC) to whole cigarette smoke followed by treatment with the viral mimetic polyinosinic polycytidylic acid (poly I:C) or influenza A virus (IAV). We found that prior smoke exposure strongly inhibited production of pro-inflammatory (interleukin 6 and interleukin 8) and anti-viral (interferon gamma induced protein 10, IP-10 and interferons) mediators in SAECs in response to poly I:C and IAV infection. Impaired antiviral responses corresponded to increased infection with IAV. This was associated with a decrease in phosphorylation of the key antiviral transcription factor interferon response factor (IRF3). Here we found that cigarette smoke exposure inhibited activation of toll-like receptor (TLR) 3 by impairing TLR3 cleavage, which was required for downstream phosphorylation of IRF3 and production of IP-10. These results identify a novel mechanism by which cigarette smoke exposure impairs antiviral responses in lung epithelial cells, which may contribute to increased susceptibility to respiratory infections.

PMID: 29351447 [PubMed - as supplied by publisher]

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