Innate immune memory in the brain shapes neurological disease hallmarks
By Ann-Christin Wendeln, Karoline Degenhardt, Lalit Kaurani, Michael Gertig, T. Ulas, Gaurav Jain, J. Wagner, Lisa M. Häsler, Katleen Wild, Angelos A. Skodras and 14 more. Nature, 2018
829 citations recorded by the source corpus.
Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished—training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months. Strikingly, in a mouse model of Alzheimer’s pathology, immune training exacerbates cerebral β-amyloidosis and immune tolerance alleviates it; similarly, peripheral immune stimulation modifies pathological features after stroke. Our results identify immune memory in the brain as an important modifier of neuropathology. Peripheral stimuli can induce acute immune training and tolerance in the brain and lead to long-lasting epigenetic reprogramming of microglia; these changes alter pathology in mouse models of stroke and Alzheimer’s pathology .
Subfields: Immunology, Neurology
View Paper: https://www.semanticscholar.org/paper/11eff9c13afe8f298fc6cc259e31c160d085f660
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Citations in the corpus
- Human Monocyte Subsets and Phenotypes in Major Chronic Inflammatory Diseases (2019, background): “In a larger consortium led by the Neher group, we recently provided evidence that a systemic immune response to LPS stimulation can lead to localized immune training in the brain (149).”
- The Role of Short-Chain Fatty Acids From Gut Microbiota in Gut-Brain Communication (2020, background): “It is now widely known that peripheral insults that cause a systemic inflammatory response might affect ongoing inflammation in the CNS mainly by microglial activation, production of inflammatory molecules, as well as recruitment of peripheral immune cells into the brain, thus shaping a cerebral inf”