# Anti-fungal immune responses in the female reproductive tract

> **NIH NIH F32** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $76,108

## Abstract

Project Summary
Vulvovaginal candidiasis (VVC) represents a global health burden and an unmet clinical need. Vulvovaginal
infection with the fungal commensal organism Candida albicans, unlike at other sites of infection, occurs in
immunocompetent women. Remarkably, VVC has a prevalence of greater than 75%, and 15% of women
experience recurrent infections, cumulatively resulting in significant cost burdens and decreases in quality of life.
As there are currently no FDA-approved vaccines for any fungal pathogen, a greater understanding of the
determinants of a protective anti-fungal immune response is a necessity. Many protective mechanisms have
been identified for systemic, oral, and cutaneous C. albicans infection, but comparatively little is understood
about tissue-specific protection at the vaginal mucosa. In murine models of VVC, mice are administered
exogenous estrogen to render them susceptible to intravaginal infection with C. albicans, to which they are
normally naïve. This is consistent with the increased susceptibility to VVC in humans, as infection is most
common in post-pubescent and pre-menopausal women who have relatively higher estrogen levels. Type 3
cytokines (IL-17 family members and IL-22) are robustly induced in VVC and in non-vaginal sites are required
for protective immune responses. However, in the case of VVC, the importance of type 3 cytokines has been
controversial. Our lab and others have found that individual deletion of type 3 cytokines, their receptors/signaling
adaptors, or inducers (Il17ra, Il22, Act1, or Il23p19) had little impact on VVC susceptibility. New data from our
lab reveals that the combined actions of type 3 cytokines are required to protect from vaginal fungal infection,
even without the induction of pseudoestrus. The proposed aims will determine the cellular and molecular
basis for how type 3 cytokine signaling orchestrates immune control of VVC. Overall, this work will help
address the substantial lack of knowledge regarding host factors required for protective immune responses
against VVC and will help clarify a long-standing misconception in the field regarding the necessity of type 3
cytokines. Ultimately, these findings could help inform vaccine and therapeutic design for a prevalent and
burdensome infection.

## Key facts

- **NIH application ID:** 10994281
- **Project number:** 1F32AI186291-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Melissa Erin Cook
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $76,108
- **Award type:** 1
- **Project period:** 2025-01-01 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10994281

## Citation

> US National Institutes of Health, RePORTER application 10994281, Anti-fungal immune responses in the female reproductive tract (1F32AI186291-01). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/10994281. Licensed CC0.

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