Research ArticleImmunology

Aging impairs both primary and secondary RIG-I signaling for interferon induction in human monocytes

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Science Signaling  12 Dec 2017:
Vol. 10, Issue 509, eaan2392
DOI: 10.1126/scisignal.aan2392

Aging compromises innate immunity

Older adults are more susceptible than younger adults to death resulting from influenza A virus (IAV) infection. Compared to monocytes from younger people, monocytes from older people produce less interferons and exhibit reduced induction of antiviral genes in response to IAV infection. Molony et al. found that this innate response to infection was compromised in cells from older individuals because of age-related changes in signaling downstream of the cytosolic RNA sensor RIG-I. Monocytes from older individuals contained less of the adaptor protein TRAF3, which is required for the induction of both interferons and the interferon regulatory transcription factor IRF8. Knocking down IRF8 compromised the interferon response of monocytes from younger individuals to RIG-I stimulation, and expressing IRF8 restored the RIG-I–induced interferon production in monocytes from older individuals. Restoring the abundance of TRAF3 or the induction of IRF8 in older individuals may therefore represent a potential therapeutic strategy for reducing age-related IAV mortality.

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