Tags

Type your tag names separated by a space and hit enter

Microglia prevent peripheral immune cell invasion and promote an anti-inflammatory environment in the brain of APP-PS1 transgenic mice.
J Neuroinflammation. 2018 Sep 21; 15(1):274.JN

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.

Authors+Show Affiliations

Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria. Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria. Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria. Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria. Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, USA.Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria. Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria.Institute of Molecular Regenerative Medicine, Paracelsus Medical University, Strubergasse 21, 5020, Salzburg, Austria. ludwig.aigner@pmu.ac.at. Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University, Salzburg, Austria. ludwig.aigner@pmu.ac.at.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30241479

Citation

Unger, M S., et al. "Microglia Prevent Peripheral Immune Cell Invasion and Promote an Anti-inflammatory Environment in the Brain of APP-PS1 Transgenic Mice." Journal of Neuroinflammation, vol. 15, no. 1, 2018, p. 274.
Unger MS, Schernthaner P, Marschallinger J, et al. Microglia prevent peripheral immune cell invasion and promote an anti-inflammatory environment in the brain of APP-PS1 transgenic mice. J Neuroinflammation. 2018;15(1):274.
Unger, M. S., Schernthaner, P., Marschallinger, J., Mrowetz, H., & Aigner, L. (2018). Microglia prevent peripheral immune cell invasion and promote an anti-inflammatory environment in the brain of APP-PS1 transgenic mice. Journal of Neuroinflammation, 15(1), 274. https://doi.org/10.1186/s12974-018-1304-4
Unger MS, et al. Microglia Prevent Peripheral Immune Cell Invasion and Promote an Anti-inflammatory Environment in the Brain of APP-PS1 Transgenic Mice. J Neuroinflammation. 2018 Sep 21;15(1):274. PubMed PMID: 30241479.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Microglia prevent peripheral immune cell invasion and promote an anti-inflammatory environment in the brain of APP-PS1 transgenic mice. AU - Unger,M S, AU - Schernthaner,P, AU - Marschallinger,J, AU - Mrowetz,H, AU - Aigner,L, Y1 - 2018/09/21/ PY - 2018/05/18/received PY - 2018/09/03/accepted PY - 2018/9/23/entrez PY - 2018/9/23/pubmed PY - 2018/12/14/medline KW - Alzheimer’s disease KW - Macrophages KW - Microglia KW - T-cells KW - TMEM119 SP - 274 EP - 274 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 15 IS - 1 N2 - 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. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/30241479/Microglia_prevent_peripheral_immune_cell_invasion_and_promote_an_anti_inflammatory_environment_in_the_brain_of_APP_PS1_transgenic_mice_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/s12974-018-1304-4 DB - PRIME DP - Unbound Medicine ER -