Innate immune memory in the brain shapes neurological disease hallmarks

Ann-Christin Wendeln, Karoline Degenhardt, Lalit Kaurani, Michael Gertig, Thomas Ulas, Gaurav Jain, Jessica Wagner, Lisa M. Häsler, Katleen Wild, Angelos Skodras, Thomas Blank, Ori Staszewski, Moumita Datta, Tonatiuh Pena Centeno, Vincenzo Capece, Md. Rezaul Islam, Cemil Kerimoglu, Matthias Staufenbiel, Joachim L. Schultze, Marc Beyer, Marco Prinz, Mathias Jucker, André Fischer and Jonas J. Neher ()
Additional contact information
Ann-Christin Wendeln: German Center for Neurodegenerative Diseases (DZNE)
Karoline Degenhardt: German Center for Neurodegenerative Diseases (DZNE)
Lalit Kaurani: University Medical Center Göttingen
Michael Gertig: University Medical Center Göttingen
Thomas Ulas: University of Bonn
Gaurav Jain: German Center for Neurodegenerative Diseases (DZNE)
Jessica Wagner: German Center for Neurodegenerative Diseases (DZNE)
Lisa M. Häsler: German Center for Neurodegenerative Diseases (DZNE)
Katleen Wild: German Center for Neurodegenerative Diseases (DZNE)
Angelos Skodras: German Center for Neurodegenerative Diseases (DZNE)
Thomas Blank: University of Freiburg
Ori Staszewski: University of Freiburg
Moumita Datta: University of Freiburg
Vincenzo Capece: German Center for Neurodegenerative Diseases (DZNE)
Md. Rezaul Islam: German Center for Neurodegenerative Diseases (DZNE)
Cemil Kerimoglu: German Center for Neurodegenerative Diseases (DZNE)
Matthias Staufenbiel: German Center for Neurodegenerative Diseases (DZNE)
Joachim L. Schultze: University of Bonn
Marc Beyer: German Center for Neurodegenerative Diseases (DZNE)
Marco Prinz: University of Freiburg
Mathias Jucker: German Center for Neurodegenerative Diseases (DZNE)
André Fischer: University Medical Center Göttingen
Jonas J. Neher: German Center for Neurodegenerative Diseases (DZNE)

Nature, 2018, vol. 556, issue 7701, 332-338

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41586-018-0023-4

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