IRF3 balances killing and cleaning

Abstract

A clean house is a sign of a boring life. When more interesting or urgent matters arise, the housework has to wait. Similarly, when the body needs to fight infection, the liver's clean-up work is impaired. Chow et al. (page 2589) now show why: switching on virus-fighting factor interferon also switches off the liver's detoxification pathway. Viral infection can cause metabolic disorders, including cholesterol and bone metabolism defects as well as Reye's syndrome, a defect in which aspirin becomes toxic because the liver fails to break it down. Liver detoxification is partly regulated by a transcription factor called retinoid X receptor (RXR), which turns on drug metabolism genes. But RXR is turned off by viral infection, Chow and colleagues now find. RXR gets down-regulated by interferon regulatory factor 3 (IRF3), the same factor responsible for promoting virus-killing interferon expression as part of the primary immune response. The team's work reveals a mechanism for crosstalk between immunity and metabolism—but why might cells need such crosstalk? “Fighting infection costs energy, and so does metabolism,” explains Chow. The simultaneous switching of resources in favor of the immune response and away from metabolism might thus be the body's way of balancing the energy budget.