# The role of platelets in protection against oral candidiasis

> **NIH NIH R01** · UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS · 2020 · $412,328

## Abstract

The role of platelets in modulation of the immune response is not completely understood. The goal of this
project is to investigate the immunomodulatory role of platelets in oropharyngeal candidiasis (OPC) caused by
Candida albicans. Normally considered for their role in clotting, platelets are also important for protection
against bacterial infection, via various mechanisms including regulation of neutrophil function. Platelets interact
with Candida, yet the consequences of this interaction during OPC are unknown. The long-term goal is to
understand the role of platelets in mucosal and disseminated fungal infection. This is a critical relationship to
understand since fungal infections are a major complication for the immunocompromised including cancer and
HIV+ patients. The overall objective of this application is to determine how platelets regulate the immune
response during OPC. The central hypothesis is that platelets are required for effective protection against
OPC. This hypothesis is based in part on preliminary data produced in the PI's laboratory. The rationale that
underlies the proposed study is that once it is known how platelets regulate oral mucosal immunity,
therapeutics involving platelets can be developed to effectively treat Candida infections. This hypothesis will be
tested in the following three specific aims: 1) Assess the role of platelets in oral clearance of C. albicans; 2)
Determine the mechanism(s) of dissemination of C. albicans after OPC; and 3) Identify how platelet deficiency
affects IL-17-mediated immunity to OPC. Collaborators have developed a mouse strain in which platelet
depletion can be induced and maintained for several weeks. In Aim 1, platelet-depleted mice will be subjected
to a well-established model of acute OPC to determine susceptibility. Preliminary data indicate susceptibility of
platelet-depleted mice to OPC, with an associated decrease in a protective neutrophil influx into the mucosa.
How platelets influence neutrophil recruitment, activation and/or neutrophil extracellular trap formation will be
determined. Preliminary data indicate that in the absence of platelets Candida disseminates to the kidney
during OPC. In Aim 2, mice will be infected to determine how platelets prevent fungus from breeching the
mucosal barrier, and if Candida is detected in the blood how platelets contribute to clearance. In Aim 3, flow
cytometry will be employed to determine the cell populations regulated by platelets during OPC. IL-17,
produced by innate lymphocytes including γδ-T cells, is necessary for protection against acute OPC, via
downstream regulation of neutrophils and defensins. How platelets intersect with the IL-17-pathway is
unknown. Platelets regulate γδ-T cells cells in other systems including melanoma, and preliminary data show
that Il17 transcript and γδ-T cells in tongue are significantly reduced in platelet-depleted mice compared to wild
type. The approach of this study is innovative, because it shifts...

## Key facts

- **NIH application ID:** 9832646
- **Project number:** 5R01DE027343-02
- **Recipient organization:** UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
- **Principal Investigator:** Heather Raquel Conti
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $412,328
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9832646

## Citation

> US National Institutes of Health, RePORTER application 9832646, The role of platelets in protection against oral candidiasis (5R01DE027343-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9832646. Licensed CC0.

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