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

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 RORɣt with eosinophil IL-17 expression. Following A. fumigatus stimulation, a population of lung eosinophils expressed RORɣt, the master transcription factor for IL-17 regulation. Eosinophil RORɣt expression was demonstrated by flow cytometry, confocal microscopy, western blotting and an mCherry reporter mouse. Both nuclear and cytoplasmic localization of RORɣt 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 RORɣt, expression of RORɣt 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, RORɣt and IL-23R. However, IL-23 is dispensable for production of IL-17 and RORɣt. Author summary: Humans regularly inhale spores of Aspergillus fumigatus, a common environmental fungus. While such exposure is of little consequence to most, in persons with impaired immune systemsit can cause a spectrum of diseases ranging from invasive aspergillosis to allergic aspergillosis. A type of white blood cell called the eosinophil is a defining feature of allergic aspergillosis. Despite their importance, the contribution of eosinophils to this disease state is poorly understood. We previously demonstrated that eosinophils produce the cytokine IL-17 in murine models of aspergillosis models. Here, we defined the contributions of two molecules, the transcription factor RORɣt and the cytokine IL-23, to eosinophil IL-17 production. These two molecules are important for optimal IL-17 production in other cell types. We discovered a population of lung eosinophils express RORɣt. While expression of the receptor for IL-23 (IL-23R) was positively correlated with expression of RORɣt, using mice deficient in IL-23, we showed IL-23 was not required for expression of RORɣt and IL-17. Thus, challenge of lungs with live A. fumigatus or its antigens skews lung eosinophils towards IL-17 production by a pathway that is independent of IL-23. Our results advance our understanding of eosinophil plasticity and have implications for the development of therapeutic approaches for treating allergic lung diseases. [ABSTRACT FROM AUTHOR]