Autocrine IL-17A–IL-17RC neutrophil activation in fungal infections is regulated by IL-6, IL-23, RORγt and Dectin-2

Here we identified a population of bone marrow neutrophils that constitutively express RORγt and which can produce and respond to IL-17A (IL-17). IL-6, IL-23 and RORγt, but not T cells or NK cells, are required for IL-17 production in neutrophils. IL-6 and IL-23 induced IL-17RC and Dectin-2 expression in neutrophils, and expression of IL-17RC was augmented by Aspergillus and Dectin-2 activation. Autocrine IL-17A–IL-17 receptor activity induced production of reactive oxygen species (ROS), and increased fungal killing in vitro and in a model of Aspergillus keratitis. Human neutrophils also expressed RORγt, and induced IL-17A, IL-17RC and Dectin-2 expression following IL-6 and IL-23 stimulation. These findings identify a population of human and murine neutrophils that exhibit autocrine IL-17 activity, and which likely contribute to the etiology of microbial and inflammatory diseases.