# Candida auris extracellular vesicles subvert host immune responses

> **NIH NIH R21** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2022 · $252,000

## Abstract

SUMMARY
There are an ~150 deaths/hour due to mycoses. This underscores the knowledge gap in our understanding of
the pathobiology of these predators, which is impeding our ability to more effectively combat invasive mycoses.
We and others have demonstrated that extracellular vesicles (EV) are key modulators of the host immune
response. The preliminary data for this R21 shows that C. auris EV directly and profoundly impede the
activation of CD4+ T cells. The suppression of T cell activation may be an important facet in the explanation for
C. auris' remarkable capacity to persist in the host. To more rigorously characterize this immunosuppressive
interaction, we will robustly characterize the inhibitory effects and determine the mechanism(s) for this
biological activity. The first Aim will define the inhibitory effect of EV from several C. auris strains on the
activation of CD4+ and CD8+ T cells and determine the nature of the inhibitory compound(s). Our preliminary
data shows that the presence of EV from C. auris significantly reduces pro-inflammatory cytokine secretion by
activated CD4+ T cells and blocks proliferation of CD4+ T cells from activated OTII mice with an antigen
presenting cell or directly, by the use of anti-CD3/anti-CD28 beads. We will also determine the nature of the
inhibitory compound(s) packaged within the C. auris EV. The second Aim will define the mechanism(s) for the
immunosuppressive effect of extracellular vesicles on T cells. We will identify which of the main pathways in T
cells are altered by EV from C. auris through an examination of signaling from the upstream CD3 complex
through to the transcription factors responsible for the polarization of T cell response towards different
phenotypes, and we will characterize the cytokines secreted by these cells. Our preliminary data suggests that
EV from C. auris have a direct effect on CD4+ T cells, which can bypass the antigen presentation step.
Identifying the mechanism of action of EV along with the compound(s) responsible for the biological effects
may have a marked impact on approaches to combatting fungal infections as well as addressing other
diseases, such as autoimmune process.

## Key facts

- **NIH application ID:** 10470876
- **Project number:** 5R21AI156104-02
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** JOSHUA D NOSANCHUK
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $252,000
- **Award type:** 5
- **Project period:** 2021-08-17 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470876

## Citation

> US National Institutes of Health, RePORTER application 10470876, Candida auris extracellular vesicles subvert host immune responses (5R21AI156104-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10470876. Licensed CC0.

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