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

Yadav, Bhawna
Specht, Charles A
Lee, Chrono K.
Pokrovskii, Maria
Huh, Jun R.
Littman, Dan R.
Levitz, Stuart M
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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 RORgammat with eosinophil IL-17 expression. Following A. fumigatus stimulation, a population of lung eosinophils expressed RORgammat, the master transcription factor for IL-17 regulation. Eosinophil RORgammat expression was demonstrated by flow cytometry, confocal microscopy, western blotting and an mCherry reporter mouse. Both nuclear and cytoplasmic localization of RORgammat 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 RORgammat, expression of RORgammat and IL-17 was similar when comparing lung eosinophils from A. fumigatus-challenged wild-type and IL-23p19-/- mice. Thus, in allergic and acute models of pulmonary aspergillosis, lung eosinophils express IL-17, RORgammat and IL-23R. However, IL-23 is dispensable for production of IL-17 and RORgammat.

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Yadav B, Specht CA, Lee CK, Pokrovskii M, Huh JR, Littman DR, Levitz SM. Lung eosinophils elicited during allergic and acute aspergillosis express RORγt and IL-23R but do not require IL-23 for IL-17 production. PLoS Pathog. 2021 Aug 31;17(8):e1009891. doi: 10.1371/journal.ppat.1009891. PMID: 34464425; PMCID: PMC8437264. Link to article on publisher's site

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DOI
10.1371/journal.ppat.1009891
PubMed ID
34464425
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Copyright © 2021 Yadav et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.