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The most evolutionarily ancient type of immunity, called “innate,” exists in all living multicellular species. When exposed to pathogens or cellular damage, cells of an organism's innate immune system activate responses that coordinate defense against the insult, and enhance the repair of tissue injury. There is a modern-day cost associated with these processes, however, because innate mechanisms can damage normal tissue and organs, potentially killing the host. Human life is a balance between dual threats of insufficient innate immune responses—which would allow pathogens to prevail—and overabundant innate immune responses—which would kill or impair directly. What has been the key to maintaining this balance throughout years of mammalian evolution? On page 729 of this issue, Sun et al. (1) report that neurons in a nematode worm can regulate innate immunity, a mechanism dating back to the early origins of the nervous system itself.