# Candida albicans oral infection shapes innate immunity and recruitment of myeloid-derived suppressor cells

> **NIH NIH R01** · STATE UNIVERSITY OF NEW YORK AT BUFFALO · 2022 · $380,000

## Abstract

Project Summary
Candida albicans is a fungal commensal organism that causes oropharyngeal candidiasis (OPC) and
may disseminate systemically in immune compromised people. However, most healthy people have
oral
levels of C. albicans and it is a beneficial organism in the human gut microbiome. Mice infected with C.
albicans also have low numbers of oral fungi but have much higher numbers of
C. albicans in the gut so
that they are a good model to study what factors permit fungal tolerance at human mucosal sites.
C. albicans hyphae secrete the aspartyl protease Sap6 that mediates virulence in OPC, induces cytokine
release from oral epithelial cells, and initiates neutrophil recruitment. Oral infection by C. albicans in mice
caused recruitment of neutrophil “swarms” surrounding invading hyphae, as well as localized Arginase1
positive (Arg1+) granulocytic cells. These Arg1+ cells showed suppression of T cells thus identifying them
as myeloid-derived suppressor cells (MDSC). MDSCs have a well-known immunosuppressive role in
cancer causing tumor immune evasion, but also have a major role in host immune responses to bacterial
and fungal infections by favoring pathogen persistence and chronic infection. We are the first to identify
MDSC recruitment upon C. albicans oral infection but we do not know their role here. C. albicans infection
resulted in changes the oral epithelium (Ep) including expression of kallikrein (KLK5) proteases
accompanying increased Ep desquamation, and increased levels of tissue Arginase 1 (Arg1). The Aims
of this project are to 1) Identify in what manner Arg1 and KLK5 expression in oral Ep alters C. albicans
infection by examining the effect of Arg1 and KLK5 depletion; 2) Determine how C. albicans induces
neutrophil swarming and recruitment of MDSCs in vitro by using live imaging of neutrophil swarming
induced by C. albicans and Sap6 and to measure fungicidal activity of MDSCs; and 3) Ascertain the
contribution of MDSCs in oral and gut Ca infection in vivo by comparing C. albicans infection in tongue
and intestine following MDSC depletion or adoptive transfer of MDSCs. The goal of this proposal is to
determine the function of MDSCs in mucosal immunity as well as how Arginase metabolites and KLK5
expression control the final outcome of fungal infection. It is proposed that MDSCs are a novel and
unexplored arm of oral epithelial immunity that contribute to oral or gut tolerance of fungal pathogens.
The long-range goal of this project is to understand host response to C. albicans and that will guide future
strategies to reduce the immune escape of C. albicans and add to our understanding of host tolerance.

## Key facts

- **NIH application ID:** 10501899
- **Project number:** 1R01DE032058-01
- **Recipient organization:** STATE UNIVERSITY OF NEW YORK AT BUFFALO
- **Principal Investigator:** Mira Edgerton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $380,000
- **Award type:** 1
- **Project period:** 2022-07-14 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10501899

## Citation

> US National Institutes of Health, RePORTER application 10501899, Candida albicans oral infection shapes innate immunity and recruitment of myeloid-derived suppressor cells (1R01DE032058-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10501899. Licensed CC0.

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