Microglial Priming as Trained Immunity in the Brain
Michael J Haley1, David Brough1, Jessica Quintin2
1Division of Neuroscience and Experimental Psychology, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, The University of Manchester, Manchester M13 9PT, UK.
Abstract:
In this review we discuss the possibility that the phenomenon of microglial priming can be explained by the mechanisms that underlie trained immunity. The latter involves the enhancement of inflammatory responses by epigenetic mechanisms that are mobilized after first exposure to an inflammatory stimulus. These mechanisms include long-lasting histone modifications, including H3K4me1 deposition at latent enhancer regions. Although such changes may be beneficial in peripheral infectious disease, in the context of microglial priming they may drive increased microglia reactivity that is damaging in diseases of brain aging.
Insights
Microglial priming, the heightened reactivity of brain immune cells, may be explained by trained immunity mechanisms. These epigenetic changes, while beneficial in infections, can harm brain aging diseases.
Area of Science:
- Neuroimmunology
- Epigenetics
- Aging Research
Background:
- Microglial priming describes enhanced brain immune cell reactivity.
- Trained immunity involves epigenetic reprogramming of inflammatory responses after initial stimuli.
Purpose of the Study:
- To explore the hypothesis that trained immunity mechanisms underlie microglial priming.
- To investigate the role of epigenetic modifications in microglial priming and brain aging.
Main Methods:
- Review of existing literature on microglial priming and trained immunity.
- Discussion of epigenetic mechanisms, including histone modifications like H3K4me1 deposition.
Main Results:
- Trained immunity offers a potential explanation for microglial priming.
- Epigenetic changes, such as H3K4me1, may drive detrimental microglia reactivity in aging.
Conclusions:
- The mechanisms of trained immunity could explain microglial priming.
- While potentially protective against peripheral infections, these epigenetic changes may exacerbate neuroinflammation in aging brains.
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