Lung eosinophils elicited during allergic and acute aspergillosis express RORϪt and IL-23R but do not require IL-23 for IL-17 production

Abstract

Exposure to the mold, Aspergillus, is ubiquitous and generally has no adverse consequences in immunocompetent persons. However, invasive and allergic aspergillosis can develop in immunocompromised and atopic individuals, respectively. Previously, we demonstrated that mouse lung eosinophils produce IL-17 in response to stimulation by live conidia and antigens of A. fumigatus. Here, we utilized murine models of allergic and acute pulmonary aspergillosis to determine the association of IL-23, IL-23R and RORϪt with eosinophil IL-17 expression. Following A. fumigatus stimulation, a population of lung eosinophils expressed RORϪt, the master transcription factor for IL-17 regulation. Eosinophil RORϪt expression was demonstrated by flow cytometry, confocal microscopy, western blotting and an mCherry reporter mouse. Both nuclear and cytoplasmic localization of RORϪt in eosinophils were observed, although the former predominated. A population of lung eosinophils also expressed IL-23R. While expression of IL-23R was positively correlated with expression of RORϪt, expression of RORϪt and IL-17 was similar when comparing lung eosinophils from A. fumigatus-challenged wild-type and IL23p19-/- mice. Thus, in allergic and acute models of pulmonary aspergillosis, lung eosinophils express IL-17, RORϪt and IL-23R. However, IL-23 is dispensable for production of IL-17 and RORϪt.