A One-Two Punch

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Science  29 Jun 2012:
Vol. 336, Issue 6089, pp. 1621
DOI: 10.1126/science.336.6089.1621-c

It's well known that viral infection can leave you susceptible to bacterial infections—a bad cold or flu followed by pneumonia is a well-known and oft-experienced example. But why? Negishi et al. now reveal a potential mechanism. They find that triggering of RIG-I–like receptors (RLRs), which are most often triggered by viruses, can inhibit Toll-like receptor (TLR) signaling, which is essential for some antibacterial responses. In particular, RLR signaling induces the transcription factor IRF3, which binds to and blocks the transcriptional activation of Il12b. Il12b encodes the p40 subunit of the cytokine interleukin-12—a molecule very important to the defense against bacterial infections. In mice, activation of RLRs led to attenuated TLR signaling and consequently, decreased T cell responses dependent on IL-12 and another cytokine that uses p40, IL-23. The consequence of such reduced immunity was that mice succumbed to sublethal doses of a bacterial infection if they were first infected with a virus.

Nat. Immunol. 13, 659 (2012).

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