期刊
JOURNAL OF NEUROSCIENCE
卷 35, 期 2, 页码 678-687出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.2510-14.2015
关键词
IL-1 beta; inflammasome; inflammatory caspases; macrophages; microglia
资金
- Dutch MS Research Foundation [MS12-805]
Inflammasomes are multiprotein complexes that link pathogen recognition and cellular stress to the processing of the proinflammatory cytokine interleukin-1 beta (IL-1 beta). Whereas inflammasome-mediated activation is heavily studied in hematopoietic macrophages and dendritic cells, much less is known about microglia, resident tissue macrophages of the brain that originate from a distinct progenitor. To directly compare inflammasome-mediated activation in different types of macrophages, we isolated primary microglia and hematopoietic macrophages from adult, healthy rhesus macaques. We analyzed the expression profile of NOD(nucleotide-binding oligomerization domain)-like receptors, adaptor proteins, and caspases and characterized inflammasome activation and regulation in detail. We here demonstrate that primary microglia can respond to the same innate stimuli as hematopoietic macrophages. However, microglial responses are more persistent due to lack of negative regulation on pro-IL-1 beta expression. In addition, we show that while caspase 1, 4, and 5 activation is pivotal for inflammasome-induced IL-1 beta secretion by hematopoietic macrophages, microglial secretion of IL-1 beta is only partially dependent on these inflammatory caspases. These results identify key cell type-specific differences that may aid the development of strategies to modulate innate immune responses in the brain.
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