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Infiltrating myeloid cell-derived properdin markedly promotes microglia-mediated neuroinflammation after ischemic
Pin-Yi Liu1, Hui-Qin Li1, Meng-Qi Dong1
1Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, 321 Zhongshan Road, Nanjing, Jiangsu, 210008, People's Republic of China.
Journal of Neuroinflammation
|November 11, 2023
Summary
Properdin exacerbates ischemic stroke by activating microglia via Mincle. Blocking this properdin-Mincle interaction may improve stroke outcomes.
Area of Science:
- Neuroscience
- Immunology
- Stroke Research
Background:
- Myeloid cells influence ischemic stroke progression through microglial interactions.
- Properdin, a complement pathway-unrelated protein, has damage-associated molecular pattern (DAMP) properties.
- The role of properdin in post-stroke neuroinflammation mediated by microglia is not well understood.
Purpose of the Study:
- To investigate the role of properdin in microglia-mediated neuroinflammation after ischemic stroke.
- To elucidate the mechanism by which properdin modulates microglial activation and exacerbates brain injury.
Main Methods:
- Used global and myeloid-specific properdin-knockout mice subjected to transient middle cerebral artery occlusion (tMCAO).
- Employed single-cell RNA sequencing, immunofluorescence, and transcriptome sequencing to analyze properdin expression and its effects on microglia.
- Investigated the interaction between properdin and macrophage-inducible C-type lectin (Mincle) in microglia.
Main Results:
- Properdin levels increased in ischemic brains, with neutrophils and macrophages as primary sources.
- Properdin knockout attenuated microglial overactivation and inflammation in tMCAO mice.
- Properdin directly binds to microglial Mincle, activating downstream inflammatory pathways and enhancing neurotoxicity.
Conclusions:
- Properdin acts as a novel mediator between peripheral myeloid cells and microglia in ischemic stroke.
- Properdin exacerbates brain injury by activating microglia through the Mincle receptor.
- Targeting the properdin-Mincle interaction offers a potential therapeutic strategy for ischemic stroke.
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