# Host Responses to Coccidioides by Human Airway Epithelium

> **NIH NIH R21** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $252,000

## Abstract

PROJECT SUMMARY
Invasive fungal infections represent a major threat to immunocompromised patients and despite the availability of anti-
fungal antibiotics, mortality rates remain as high as 50%. In the human host, the airway epithelium is the first point of
contact upon inhalation of fungal conidia. As an immunologically active tissue, the airway epithelium may participate in
active phagocytosis and coordinated immune cell recruitment. Soil fungi, including Coccidioides, do not need a human host
to propagate, but upon disruption can enter the human body and lead to infection if not cleared. The fungal dimorph
Coccidioides is native to arid regions in the southwestern U.S. and can establish infections in both immunocompetent and
immunocompromised individuals. Unfortunately, little is known with regards to the initial response of human airway
epithelium to Coccidioides. Currently, the Δcps1 strain of Coccidioides is being investigated as a potential vaccine
candidate. Leveraging new technologies that permit the isolation of human airway stem cells, we demonstrated that primary
differentiated human airway epithelial cells recapitulate the complexity of human airways. Our preliminary data showed
infection at the apical surface of human airway epithelial cells by C. posadasii (Δcps1) elicits pro-inflammatory signals by
the epithelium. Lastly, we demonstrated effective gene knockout in primary human airway epithelial cells using non-viral
bulk nucleofection-based CRISPR strategy. Thus, our primary objective is to decipher the transcriptional and secretomal
signatures critical to mount a successful response to Coccidioides in the human airway epithelium. To address our primary
objective, we propose the following two specific aims: [1] determine the host response of human airway epithelium to both
WT and the vaccine candidate C. posadasii (Δcps1), and [2] identify key signaling pathways to elicit an immune response
to WT and the vaccine candidate C. posadasii (Δcps1) by human airway epithelium. This work will identify essential
components of the human airway epithelium to mediate a protective response to these fungal infections and will provide the
necessary foundation for future experiments to dissect the key pathways responsible for an effective host response to C.
posadasii.

## Key facts

- **NIH application ID:** 10373208
- **Project number:** 1R21AI152499-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Jatin M Vyas
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $252,000
- **Award type:** 1
- **Project period:** 2022-05-02 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10373208

## Citation

> US National Institutes of Health, RePORTER application 10373208, Host Responses to Coccidioides by Human Airway Epithelium (1R21AI152499-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10373208. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*