Priming Microglia for Innate Immune Memory in the Brain

Microglia, the resident macrophages of the brain, are highly plastic and well known to be pre-activated or 'primed' by active inflammatory processes, resulting in amplified responses to a second inflammatory insult. Furthermore, the capacity of microglia to develop 'innate immune memory' (IIM), that is, long-lasting molecular reprogramming, has recently been demonstrated. Depending on the initial stimulus, IIM can either enhance or suppress microglial responses to a delayed, secondary insult. Moreover, both priming and IIM can affect pathological hallmarks of neurological disease in mouse models, which may be consistent with certain clinical observations in patients. Here, we discuss the remarkable capacity of microglia to process inflammatory signals over short and long timeframes and propose new integrated nomenclature for these processes. We also highlight future research avenues, with implications for human brain disease.