Inhibition of phagocytosis and lysosomal acidification suppresses neurotoxic prion peptide-induced NALP3 inflammasome activation in BV2 microglia

• Inhibition of phagocytosis and lysosomal acidification suppressed NALP3 activation.
• Inhibition of phagocytosis and lysosomal acidification reduced IL-1β and IL-18 expression and release.
• Inhibition of phagocytosis and lysosomal acidification downregulated the expression of pro-inflammatory cytokines and chemotactic factors.

Prion diseases are neurodegenerative disorders characterized by the accumulation of misfolded prion protein. In a previous study, we showed that neurotoxic prion peptide (PrP106-126) induced NALP3 inflammasome activation in mouse primary and immortalized microglia. In the present work, we examined the relevance of phagocytosis and lysosomal acidification to the activation of the NALP3 inflammasome in PrP106-126-stimulated microglia. Our results showed that the inhibition of phagocytosis or lysosomal acidification significantly reduced IL-1β and IL-18 production, downregulated NALP3 and ASC expression, and decreased the expression of proinflammatory factors. We concluded that phagocytosis and lysosomal acidification are necessary for PrP106-126-induced NALP3 activation in BV2 cells.