Interleukin-10 Prevents Pathological Microglia Hyperactivation following Peripheral Endotoxin Challenge.
Immunity
; 53(5): 1033-1049.e7, 2020 11 17.
Article
em En
| MEDLINE
| ID: mdl-33049219
ABSTRACT
Microglia, the resident macrophages of the brain parenchyma, are key players in central nervous system (CNS) development, homeostasis, and disorders. Distinct brain pathologies seem associated with discrete microglia activation modules. How microglia regain quiescence following challenges remains less understood. Here, we explored the role of the interleukin-10 (IL-10) axis in restoring murine microglia homeostasis following a peripheral endotoxin challenge. Specifically, we show that lipopolysaccharide (LPS)-challenged mice harboring IL-10 receptor-deficient microglia displayed neuronal impairment and succumbed to fatal sickness. Addition of a microglial tumor necrosis factor (TNF) deficiency rescued these animals, suggesting a microglia-based circuit driving pathology. Single cell transcriptome analysis revealed various IL-10 producing immune cells in the CNS, including most prominently Ly49D+ NK cells and neutrophils, but not microglia. Collectively, we define kinetics of the microglia response to peripheral endotoxin challenge, including their activation and robust silencing, and highlight the critical role of non-microglial IL-10 in preventing deleterious microglia hyperactivation.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Interleucina-10
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Microglia
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Endotoxinas
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article