Charcot-Leyden Crystals Activate the NLRP3 Inflammasome and Cause IL-1beta Inflammation in Human Macrophages
Department of Medicine, Division of Infectious Diseases and Immunology
Immunology and Infectious Disease | Infectious Disease
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-1beta 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-1beta 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-1beta 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.
DOI of Published Version
Rodríguez-Alcázar JF, Ataide MA, Engels G, Schmitt-Mabmunyo C, Garbi N, Kastenmüller W, Latz E, Franklin BS. Charcot-Leyden Crystals Activate the NLRP3 Inflammasome and Cause IL-1β Inflammation in Human Macrophages. J Immunol. 2019 Jan 15;202(2):550-558. doi: 10.4049/jimmunol.1800107. Epub 2018 Dec 17. PMID: 30559319. Link to article on publisher's site
Journal of immunology (Baltimore, Md. : 1950)
Rodriguez-Alcazar JF, Ataide MA, Engels G, Schmitt-Mabmunyo C, Garbi N, Kastenmuller W, Latz E, Franklin BS. (2019). Charcot-Leyden Crystals Activate the NLRP3 Inflammasome and Cause IL-1beta Inflammation in Human Macrophages. Infectious Diseases and Immunology Publications. https://doi.org/10.4049/jimmunol.1800107. Retrieved from https://escholarship.umassmed.edu/infdis_pp/417