NLRP3 Inflammasome Is Expressed and Functional in Mouse Brain Microglia but Not in Astrocytes

Neuroinflammation is the local reaction of the brain to infection, trauma, toxic molecules or protein aggregates. The brain resident macrophages, microglia, are able to trigger an appropriate response involving secretion of cytokines and chemokines, resulting in the activation of astrocytes and recruitment of peripheral immune cells. IL-1 beta plays an important role in this response; yet its production and mode of action in the brain are not fully understood and its precise implication in neurodegenerative diseases needs further characterization. Our results indicate that the capacity to form a functional NLRP3 inflammasome and secretion of IL-1 beta is limited to the microglial compartment in the mouse brain. We were not able to observe IL-1 beta secretion from astrocytes, nor do they express all NLRP3 inflammasome components. Microglia were able to produce IL-1 beta in response to different classical inflammasome activators, such as ATP, Nigericin or Alum. Similarly, microglia secreted IL-18 and IL-1 alpha, two other inflammasome-linked pro-inflammatory factors. Cell stimulation with alpha-synuclein, a neurodegenerative disease-related peptide, did not result in the release of active IL-1 beta by microglia, despite a weak pro-inflammatory effect. Amyloid-beta peptides were able to activate the NLRP3 inflammasome in microglia and IL-1 beta secretion occurred in a P2X7 receptor-independent manner. Thus microglia-dependent inflammasome activation can play an important role in the brain and especially in neuroinflammatory conditions.