# Mononuclear phagocyte networks in mycobiota regulation and antifungal immunity.

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2020 · $540,252

## Abstract

Abstract
Intestinal fungi are an important component of the microbiota, and recent studies have unveiled their potential
in modulating inflammatory disease. Mucosal immunity to fungi has been largely explored in the context of oral,
skin, vaginal or lung infection. Nonetheless, the mechanisms governing immunity to gut fungi (mycobiota)
remain unknown. We have shown that a polymorphism in the human gene encoding the anti-fungal receptor
Dectin-1 (CLEC7A) is strongly associated with severity of ulcerative colitis and that, in a mouse models of
colitis and lung allergy, fungal dysbiosis can contribute to intestinal and lung inflammation. This suggests that
intestinal immunity to fungi may be an important factor in shaping host immunity.
As a central hub of mucosal immunity, the gastrointestinal tract is naturally equipped with a cellular machinery
to recognize and interact with the microbiota populating this body site. The intestines harbor several subsets of
phagocytes, which are known to respond to bacterial infections or to fluctuations in commensal bacterial
communities. These intestinal phagocyte subsets comprise of conventional dendritic cells (DCs), most of which
express the integrin CD103 albeit different levels of CD11b, and intestinal MNPs which express high levels of
CX3CR1. CX3CR1+ MNPs and CD103+ DCs have the potential to induce antigen specific T helper responses
to commensal and pathogenic bacteria in the gut. We and others have shown that Dectin-1/ CARD9 axis is
crucial for the induction of antifungal Th17 immunity at several barrier sites and can affect responses toward
intestinal mycobiota. However how intestinal phagocyte networks coordinate gut fungal sensing and immunity
to mycobiota is currently unknown.
It is becoming increasingly clear that an aberrant pro-inflammatory response to microbiota by infiltrating
monocytes plays a role in the development of intestinal inflammation. Our data show that intestinal
mononuclear phagocytes with characteristics of macrophages play an important role in limiting fungal
overgrowth in the gut, and can be influenced by the inflammatory environment to further propel inflammation.
We further show that a specific subset of CX3CR1+ gut mononuclear phagocytes (MNPs) interacts with bona-
fide gut fungi to trigger innate and adaptive immune responses to fungi. Employing conditional knock out in
vivo models, model fungal strains, high-throughput platforms for fungal and bacterial sequencing, targeting of
fungi with drugs, and computational pipelines, we will define how phagocytes control immunity to fungi in the
gut to influence states of health and inflammatory disease. Better understanding of the interaction of intestinal
phagocytes with commensal fungi, would provide an opportunity for the development of more targeted
therapies for inflammatory diseases.

## Key facts

- **NIH application ID:** 9973846
- **Project number:** 1R01DK121977-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** ILIYAN Dimitrov ILIEV
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $540,252
- **Award type:** 1
- **Project period:** 2020-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9973846

## Citation

> US National Institutes of Health, RePORTER application 9973846, Mononuclear phagocyte networks in mycobiota regulation and antifungal immunity. (1R01DK121977-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9973846. Licensed CC0.

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