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

Neutrophils are an important source of interleukin (IL)-1 beta and other cytokines because they are recruited to sites of infection and inflammation in high numbers. Although secretion of processed, bioactive IL-1 beta by neutrophils is dependent on NLRP3 and Gasdermin D (GSDMD), IL-1 alpha secretion by neutrophils has not been reported. In this study, we demonstrate that neutrophils produce IL-1 alpha following injection of Aspergillus fumigatus spores that express cell-surface beta-glucan. Although IL-1 alpha secretion by lipopolysaccharide (LPS)/ATP-activated macrophages and dendritic cells is GSDMD dependent, IL-1 alpha secretion by beta-glucan-stimulated neutrophils occurs independently of GSDMD. Instead, we found that bioactive IL-1 alpha is in exosomes that were isolated from cell-free media of beta-glucan-stimulated neutrophils. Further, the exosome inhibitor GW4869 significantly reduces IL-1 alpha in extracellular vesicles (EVs) and total cell-free supernatant. Together, these findings identify neutrophils as a source of IL-1 alpha and demonstrate a role for EVs, specifically exosomes, in neutrophil secretion of bioactive IL-1 alpha.

Automated summary

Neutrophils are shown to produce IL-1 alpha in response to beta-glucan stimulation, and the secretion of IL-1 alpha is found to be independent of GSDMD in neutrophils. Additionally, exosomes play a significant role in the release of bioactive IL-1 alpha from neutrophils.