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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

Microglia prevent peripheral immune cell invasion and promote an anti-inflammatory environment in the brain of APP-PS1 transgenic mice

Authors: M. S. Unger, P. Schernthaner, J. Marschallinger, H. Mrowetz, L. Aigner

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

Undoubtedly, neuroinflammation is a major contributor to Alzheimer’s disease (AD) progression. Neuroinflammation is characterized by the activity of brain resident glial cells, in particular microglia, but also by peripheral immune cells, which infiltrate the brain at certain stages of disease progression. The specific role of microglia in shaping AD pathology is still controversially discussed. Moreover, a possible role of microglia in the interaction and recruitment of peripheral immune cells has so far been completely ignored.

Methods

We ablated microglia cells in 12-month-old WT and APP-PS1 transgenic mice for 4 weeks using the CSF1R inhibitor PLX5622 and analyzed its consequences to AD pathology and in particular to peripheral immune cell infiltration.

Results

PLX5622 treatment successfully reduced microglia numbers. Interestingly, it uncovered a treatment-resistant macrophage population (Iba1+/TMEM119−). These cells strongly expressed the phagocytosis marker CD68 and the lymphocyte activation, homing, and adhesion molecule CD44, specifically at sites of amyloid-beta plaques in the brains of APP-PS1 mice. In consequence, ablation of microglia significantly raised the number of CD3+/CD8+ T-cells and reduced the expression of anti-inflammatory genes in the brains of APP-PS1 mice.

Conclusion

We conclude that in neurodegenerative conditions, chronically activated microglia might limit CD3+/CD8+ T-cell recruitment to the brain and that local macrophages connect innate with adaptive immune responses. Investigating the role of peripheral immune cells, their interaction with microglia, and understanding the link between innate and adaptive immune responses in the brain might be a future directive in treating AD pathology.
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Metadata
Title
Microglia prevent peripheral immune cell invasion and promote an anti-inflammatory environment in the brain of APP-PS1 transgenic mice
Authors
M. S. Unger
P. Schernthaner
J. Marschallinger
H. Mrowetz
L. Aigner
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1304-4

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