TY  - JOUR
AU  - Wendeln, Ann-Christin
AU  - Degenhardt, Karoline
AU  - Kaurani, Lalit
AU  - Gertig, Michael
AU  - Ulas, Thomas
AU  - Jain, Gaurav
AU  - Wagner, Jessica
AU  - Häsler, Lisa M
AU  - Wild, Katleen
AU  - Skodras, Angelos
AU  - Blank, Thomas
AU  - Staszewski, Ori
AU  - Datta, Moumita
AU  - Pena Centeno, Tonatiuh
AU  - Capece, Vincenzo
AU  - Islam, Rezaul
AU  - Kerimoglu, Cemil
AU  - Staufenbiel, Matthias
AU  - Schultze, Joachim L
AU  - Beyer, Marc
AU  - Prinz, Marco
AU  - Jucker, Mathias
AU  - Fischer, André
AU  - Neher, Jonas J
TI  - Innate immune memory in the brain shapes neurological disease hallmarks.
JO  - Nature 
VL  - 556
IS  - 7701
SN  - 0028-0836
CY  - London [u.a.]
PB  - Nature Publ. Group65848
M1  - DZNE-2020-06231
SP  - 332-338
PY  - 2018
AB  - 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.
KW  - Alzheimer Disease: immunology
KW  - Alzheimer Disease: pathology
KW  - Amyloidosis: immunology
KW  - Amyloidosis: pathology
KW  - Animals
KW  - Brain: immunology
KW  - Brain: pathology
KW  - Disease Models, Animal
KW  - Epigenesis, Genetic
KW  - Female
KW  - Gene Expression Regulation: immunology
KW  - Humans
KW  - Immune Tolerance
KW  - Immunity, Innate
KW  - Immunologic Memory
KW  - Inflammation: genetics
KW  - Inflammation: immunology
KW  - Male
KW  - Mice
KW  - Microglia: immunology
KW  - Microglia: metabolism
KW  - Nervous System Diseases: immunology
KW  - Nervous System Diseases: pathology
KW  - Stroke: immunology
KW  - Stroke: pathology
LB  - PUB:(DE-HGF)16
C6  - pmid:29643512
C2  - pmc:PMC6038912
DO  - DOI:10.1038/s41586-018-0023-4
UR  - https://pub.dzne.de/record/139909
ER  -