# The contribution of eosinophils and the IL-23/IL-17 axis to host responses to Aspergillus

> **NIH NIH R01** · UNIV OF MASSACHUSETTS MED SCH WORCESTER · 2020 · $418,750

## Abstract

Project Summary/Abstract
The spectrum of diseases caused by the opportunistic fungal pathogen, Aspergillus, depends in large measure
upon the immune status of the host. Over 5 million people suffer from allergic forms of aspergillosis including
allergic bronchopulmonary aspergillosis and severe asthma with fungal sensitization. Eosinophils are hallmarks
and drivers of allergic aspergillosis but the mechanisms by which eosinophils contribute to immunopathology
are not well understood. On the other end of the spectrum, invasive aspergillosis occurs mostly in severely
immunocompromised persons; over 200,000 people annually are afflicted and the mortality rate is high. The
contribution of eosinophils to immunity in invasive aspergillosis is uncertain; however, we have observed that
mice lacking eosinophils are hypersusceptible. The IL-23/IL17 axis is postulated to play a role in immune
responses to Aspergillus species and to contribute to the pathophysiology of some forms of asthma. We have
discovered that following pulmonary challenge with live Aspergillus fumigatus conidia or aerosol challenge of
sensitized mice with A. fumigatus antigens, lung eosinophils express IL-23 and IL-17. Moreover, mice lacking
eosinophils have reduced IL-23 and IL-17 in their lungs following A. fumigatus challenge. The overarching
hypotheses of this proposal are: 1) eosinophils are major drivers of the IL-23/IL-17 axis in pulmonary
aspergillosis; and 2) eosinophilic production of IL-23 and IL-17 is protective in invasive aspergillosis but
detrimental in allergic aspergillosis. Our interrelated specific aims will test these hypotheses. Aim 1 is to
determine the drivers and consequences of eosinophil production of IL-23/IL-17 in allergic and invasive
aspergillosis. We hypothesize that eosinophil expression of IL-23 and IL-17, driven by signaling through C-type
lectin receptors, informs immunological responses and outcome in IPA and APA. Aim 2 is to assess the
contribution of IL-23R and RORγt to the phenotype of IL-17+/IL-23+ lung eosinophils elicited in response to live
Aspergillus and Aspergillus antigens. We postulate that in the setting of Aspergillus stimulation, eosinophils
respond to autocrine IL-23 via the IL-23R which turns on expression of the transcription factor RORγt leading
to IL-17 expression. Aim 3 is to elucidate cellular targets of eosinophil IL-23/IL-17 responsible for innate and
adaptive immune responses. Mechanistic insights into how eosinophil IL-23 and IL-17 expression informs
innate and adaptive immunity to Aspergillus will be garnered as we test the hypothesis that lung epithelial cells
and T cells are cellular targets of eosinophil-derived IL-17 and IL-23, respectively. Successful completion of the
proposed hypothesis-driven studies will have a large overall impact on our understanding of eosinophil biology,
the IL-23/IL-17 axis, and the immunology of invasive and allergic forms of aspergillosis. The project has
translational significance as the res...

## Key facts

- **NIH application ID:** 9964495
- **Project number:** 5R01AI139615-03
- **Recipient organization:** UNIV OF MASSACHUSETTS MED SCH WORCESTER
- **Principal Investigator:** Stuart Michael Levitz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $418,750
- **Award type:** 5
- **Project period:** 2018-07-11 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964495

## Citation

> US National Institutes of Health, RePORTER application 9964495, The contribution of eosinophils and the IL-23/IL-17 axis to host responses to Aspergillus (5R01AI139615-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9964495. Licensed CC0.

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