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Publication : β-Glucan-stimulated neutrophil secretion of IL-1α is independent of GSDMD and mediated through extracellular vesicles.

First Author  Ratitong B Year  2021
Journal  Cell Rep Volume  35
Issue  7 Pages  109139
PubMed ID  34010648 Mgi Jnum  J:317355
Mgi Id  MGI:6717017 Doi  10.1016/j.celrep.2021.109139
Citation  Ratitong B, et al. (2021) beta-Glucan-stimulated neutrophil secretion of IL-1alpha is independent of GSDMD and mediated through extracellular vesicles. Cell Rep 35(7):109139
abstractText  Neutrophils are an important source of interleukin (IL)-1beta and other cytokines because they are recruited to sites of infection and inflammation in high numbers. Although secretion of processed, bioactive IL-1beta by neutrophils is dependent on NLRP3 and Gasdermin D (GSDMD), IL-1alpha secretion by neutrophils has not been reported. In this study, we demonstrate that neutrophils produce IL-1alpha following injection of Aspergillus fumigatus spores that express cell-surface beta-glucan. Although IL-1alpha secretion by lipopolysaccharide (LPS)/ATP-activated macrophages and dendritic cells is GSDMD dependent, IL-1alpha secretion by beta-glucan-stimulated neutrophils occurs independently of GSDMD. Instead, we found that bioactive IL-1alpha is in exosomes that were isolated from cell-free media of beta-glucan-stimulated neutrophils. Further, the exosome inhibitor GW4869 significantly reduces IL-1alpha in extracellular vesicles (EVs) and total cell-free supernatant. Together, these findings identify neutrophils as a source of IL-1alpha and demonstrate a role for EVs, specifically exosomes, in neutrophil secretion of bioactive IL-1alpha.
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