[HTML][HTML] IRF3 mediates a TLR3/TLR4-specific antiviral gene program

SE Doyle, SA Vaidya, R O'Connell, H Dadgostar… - Immunity, 2002 - cell.com
SE Doyle, SA Vaidya, R O'Connell, H Dadgostar, PW Dempsey, TT Wu, G Rao, R Sun
Immunity, 2002cell.com
We have identified a subset of genes that is specifically induced by stimulation of TLR3 or
TLR4 but not by TLR2 or TLR9. Further gene expression analyses established that
upregulation of several primary response genes was dependent on NF-κB, commonly
activated by several TLRs, and interferon regulatory factor 3 (IRF3), which was found to
confer TLR3/TLR4 specificity. Also identified was a group of secondary response genes
which are part of an autocrine/paracrine loop activated by the primary response gene …
Abstract
We have identified a subset of genes that is specifically induced by stimulation of TLR3 or TLR4 but not by TLR2 or TLR9. Further gene expression analyses established that upregulation of several primary response genes was dependent on NF-κB, commonly activated by several TLRs, and interferon regulatory factor 3 (IRF3), which was found to confer TLR3/TLR4 specificity. Also identified was a group of secondary response genes which are part of an autocrine/paracrine loop activated by the primary response gene product, interferon β (IFNβ). Selective activation of the TLR3/TLR4-IRF3 pathway potently inhibited viral replication. These results suggest that TLR3 and TLR4 have evolutionarily diverged from other TLRs to activate IRF3, which mediates a specific gene program responsible for innate antiviral responses.
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