Charcot–Leyden Crystals Activate the NLRP3 Inflammasome and Cause IL-1β Inflammation in Human Macrophages

Charcot–Leyden crystals (CLCs) are Galectin-10 protein crystals that can form after eosinophils degranulate. CLCs can appear and persist in tissues from patients with eosinophilic disorders, such as asthma, allergic reactions, and fungal and helminthic infections. Despite abundant reports of their occurrence in human disease, the inflammatory potential of CLCs has remained unknown. In this article, we show that CLCs induce the release of the proinflammatory cytokine IL-1β upon their phagocytosis by primary human macrophages in vitro. Chemical inhibition and small interfering RNA knockdown of NLRP3 in primary human macrophages abrogated their IL-1β response to CLCs. Using C57BL/6 ASC-mCitrine transgenic inflammasome reporter mice, we showed that the instillation of CLCs into the lungs promoted the assembly of ASC complexes in infiltrating immune cells (neutrophils and inflammatory monocytes) and resulted in IL-1β accumulation into the bronchoalveolar lavage fluid. Our findings reveal that CLCs are recognized by the NLRP3 inflammasome, which may sustain inflammation that follows eosinophilic inflammatory processes.