Adaptive immune cells are not the only immune cells that have some form of memory - innate immune cells do too. Certain immune stimuli ‘train’ blood monocytes and enhance the immune response to subsequent challenges, whereas others suppress inflammation and induce tolerance. Innate immune memory is mediated by epigenetic reprogramming and can last for months in circulating monocytes. Here, Jonas Neher and colleagues show that peripherally applied inflammatory stimuli also induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of long-lived brain-resident macrophages; microglia. The changes last for at least six months. Importantly, in a mouse model of Alzheimer’s disease pathology, immune training exacerbates cerebral amyloidosis, whereas tolerance alleviates it. Similarly, peripheral immune stimulation modifies pathological features after stroke. These findings show that immune memory in the brain is an important modifier of neuropathology.
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