Innate immune memory in the brain shapes neurological disease hallmarks
Abstrak
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 .
Topik & Kata Kunci
Penulis (24)
Ann-Christin Wendeln
Karoline Degenhardt
Lalit Kaurani
Michael Gertig
T. Ulas
Gaurav Jain
J. Wagner
Lisa M. Häsler
Katleen Wild
Angelos A. Skodras
T. Blank
O. Staszewski
Moumita Datta
Tonatiuh Peña Centeno
Vincenzo Capece
M. Islam
C. Kerimoglu
M. Staufenbiel
J. Schultze
M. Beyer
M. Prinz
M. Jucker
A. Fischer
J. Neher
Akses Cepat
- Tahun Terbit
- 2018
- Bahasa
- en
- Total Sitasi
- 793×
- Sumber Database
- Semantic Scholar
- DOI
- 10.1038/s41586-018-0023-4
- Akses
- Open Access ✓