Innate immune cells act as a surveillance system, detecting and responding to pathogens and endogenous danger signals. The complex patterns of signals they receive are detected by a variety of pattern recognition receptors (PRRs). On page 1232 of this issue, Zanoni et al. (1) find that innate immune responses to microbial products do not occur in a vacuum; rather, there is a complex array of danger signals in surrounding damaged tissue that can determine an immune cell type–specific response to pathogens. They describe a host-derived lipid that binds to a PRR to induce a hyperactive innate immune response that enhances long-lived protective immunity against invading microbes.
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