Mucosal host defense against vaginal candidiasis

NIH RePORTER · NIH · R21 · $236,730 · view on reporter.nih.gov ↗

Abstract

ABSTRACT Vulvovaginal candidiasis (VVC) is a widespread mucosal infection caused predominantly by the commensal fungus Candida albicans. VVC is a global health concern due to its high prevalence in immunocompetent women (>75% incidence). Although not fatal, approximately 15% of women experience VVC recurrently, resulting in serious impacts on quality of life and significant cost burden. There are no licensed vaccines to any fungal pathogens. While much has been learned about immunity to C. albicans in other sites (mouth, gut, skin), our understanding of immunity at the vaginal mucosa is comparatively limited. Control of C. albicans in mouth and skin unquestionably requires Th17 cells/IL-17, but the role of the Th17 pathway in VVC is controversial. Women with HIV/AIDS or rare Th17/IL-17 receptor genetic deficiencies are not thought to have abnormal incidences of VVC, yet Th17 signatures are upregulated in VVC, and VVC is a statistically significant adverse event associated with IL-17 or other anti-cytokine blockade. Here we show that multiple cytokines in the Th17 axis act in concert to promote immunity to VVC, and we will probe the essential correlates that drive immunity in this mucosal setting from both the host and the fungal side.

Key facts

NIH application ID
10942918
Project number
1R21AI185365-01
Recipient
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Principal Investigator
Sarah L Gaffen
Activity code
R21
Funding institute
NIH
Fiscal year
2024
Award amount
$236,730
Award type
1
Project period
2024-06-21 → 2026-04-30