# Fungal Asthma and Lung Innate Immunity

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $517,581

## Abstract

Abstract:
Environmental mold (fungal) exposure has long been recognized as a critical risk factor for asthma and asthma
exacerbation. The prevalence of fungal sensitization can be up to 48% in asthmatics and fungal asthma is
oftentimes poorly managed with frequent exacerbations and hospitalizations. Efforts to reduce indoor fungal
exposure by cleaning have been proven impossible in the recent HEAL study. However, an average person
exposing to a large number of fungal spores each day, up to 50,000 spores per cubic meter of air during the
fungal season, has no detectable respiratory abnormality and not all individuals with fungal sensitization
develop asthma. Thus, it is significant to understand the mechanistic basis of this resilience to maintain airway
homeostasis despite the impact of abundant asthmagenic substances produced by fungi. Interestingly, IFN
signatures were discovered in the fungal asthma model using live Alternaria spores. Epithelial cells were found
to sense fungal spores by triggering IFN-I/III production as well as their downstream signaling cascades. IFN-I
receptor blockade or deficiency augmented asthmatic phenotypes, suggesting a protective role of IFN-I against
asthma. Thus, our overall hypothesis is that fungal spore sensing activates protective IFN-I/III pathway and the
impairment of this protection leads to asthma. To test this hypothesis, we will elucidate the protective function
of IFN-I/III in the fungal asthma model using a set of knockout mice. Then, we will determine the mechanistic
basis of fungal detection and innate defense. Finally yet importantly, we will examine IFN signatures in clinical
samples from human asthma with or without fungal sensitization by utilizing datasets and samples from a NIH-
supported Asthma Research Program. The completion of this proposal will advance our knowledge about the
pathogenesis of fungal asthma, and establish a foundation for the further therapeutic development to treat this
type of asthma.

## Key facts

- **NIH application ID:** 10056131
- **Project number:** 1R01AI149754-01A1
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Yin Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $517,581
- **Award type:** 1
- **Project period:** 2020-05-07 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056131

## Citation

> US National Institutes of Health, RePORTER application 10056131, Fungal Asthma and Lung Innate Immunity (1R01AI149754-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10056131. Licensed CC0.

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