# Dectin-1 Signaling Mechanisms

> **NIH NIH R01** · CEDARS-SINAI MEDICAL CENTER · 2021 · $533,266

## Abstract

SUMMARY/ABSTRACT
Dectin-1 is an innate immune receptor expressed by myeloid phagocytes such as macrophages and dendritic
cells that is essential for effective host defense against fungal infections. Dectin-1 recognizes the β-1,3-glucan
polysaccharide that makes up as much as half the dry weight of fungal cell walls, and activation of the receptor
triggers phagocytosis, production of microbicidal reactive oxygen species, and production of a host of pro-
inflammatory cytokines. Dectin-1 is one of only a few receptors so far shown to be sufficient for triggering
phagocytosis, and it has thus become an important model for understanding how such receptors work. This
renewal project focuses on further understanding the mechanisms of Dectin-1 signaling. Previous studies have
documented that Dectin-1 signaling in response to common yeast such as Candida albicans promotes IL-23
production by dendritic cells that, together with other inflammatory mediators, supports a good Th1/Th17 T cell
response. This response is essential for mucosal immunity to fungal infections. In contrast, we now observe that
C. albicans hyphae activate dendritic cells to drive a response better characterized as Th2/Th9 and that Dectin-
1 is also critical for this response. Further, we note that colonization with certain fungi including Candida spp.
and Wallemia spp. exacerbate Th2/9-driven mouse models of allergic airway disease. In this project, we will
investigate the mechanisms by which the Dectin-1 signaling pathway promotes Th2 and Th9 type immune
responses in vitro and in vivo. We will further develop novel strategies for pharmacologically manipulating this
signaling pathway.

## Key facts

- **NIH application ID:** 10162482
- **Project number:** 5R01AI071116-12
- **Recipient organization:** CEDARS-SINAI MEDICAL CENTER
- **Principal Investigator:** David M. Underhill
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $533,266
- **Award type:** 5
- **Project period:** 2008-01-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162482

## Citation

> US National Institutes of Health, RePORTER application 10162482, Dectin-1 Signaling Mechanisms (5R01AI071116-12). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10162482. Licensed CC0.

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