# Dissecting the impact of immune environment on Candida albicans pathogenic potential in the gut

> **NIH NIH DP2** · UNIVERSITY OF COLORADO DENVER · 2024 · $46,535

## Abstract

PROJECT SUMMARY
The human gut microbiome harbors microbes with the capacity to cause infection or drive pathogenic
inflammation. Immune status often determines risk for microbiome-associated disease, which is typically
attributed to immune impacts on microbial community composition. But pathogenic or commensal lifestyles can
also be dynamically regulated within individual microbes, and there is far less understood about immune
impacts on microbial inherent pathogenic potential. Candida albicans is a morphologically and transcriptionally
dynamic commensal fungus that can cause life-threatening infections and exacerbate pathogenic
inflammation. The ability for C. albicans to cause disease depends on its phenotypic state. Of particular
importance is the formation of hyphae, which are elongated cells specialized for adherence and invasion, and
promote disease in both infection and inflammatory settings. Immune status is crucial for determining risk for
C. albicans-associated disease and both immune deficiencies and active inflammation are linked to C. albicans
pathogenesis. However, the role of immune environment on in vivo C. albicans pathogenic potential is not well
understood. Here, I will investigate the impact of two human relevant immune environments on C. albicans
pathogenic potential. Project 1 will focus on IgA regulation of C. albicans biology. Anti-C. albicans IgA
antibodies are found in the gut of most people, and I previously found that C. albicans hyphae and associated
effectors are heavily targeted by IgA during colonization. In mouse models, IgA targeting is associated with
reduced hyphae and reduced capacity to exacerbate colitis. Here, I will interrogate mechanisms by which IgA
regulates C. albicans biology in vivo using a mouse colonization model that permits investigation of immediate
regulatory impacts of IgA targeting on C. albicans biology. Using this model, I will interrogate IgA impacts on C.
albicans morphology and gene expression, which will include single cell transcriptional profiling to investigate
gene expression in individual IgA-targeted cells. The goal of Project 2 is to define the impacts of inflammation
on C. albicans pathogenic potential. Evidence from human IBD studies and mouse models of colitis suggest
that this fungus exploits inflammation to bloom and perpetuate disease. Here, I will use a mouse model of
intestinal colitis to define inflammation-dependent impacts on C. albicans morphology and transcriptional
profile, with the goal of defining C. albicans pathways responsible for disease exacerbation. This proposal will
reveal fundamental mechanisms by which immune environment regulates C. albicans biology and advance our
understanding of how C. albicans becomes pathogenic in certain people. Broadly, these efforts will provide a
foundation for our long-term goal of identifying targeted therapeutic strategies to prevent commensal C.
albicans reservoirs from causing disease.

## Key facts

- **NIH application ID:** 10938526
- **Project number:** 3DP2AI177927-01S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kyla Ost
- **Activity code:** DP2 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $46,535
- **Award type:** 3
- **Project period:** 2023-09-01 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938526

## Citation

> US National Institutes of Health, RePORTER application 10938526, Dissecting the impact of immune environment on Candida albicans pathogenic potential in the gut (3DP2AI177927-01S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10938526. Licensed CC0.

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