# Dendritic cell heterogeneity and its role in pulmonary fungal infection

> **NIH NIH F30** · WEILL MEDICAL COLL OF CORNELL UNIV · 2021 · $48,291

## Abstract

Project Summary
The opportunistic fungal pathogen Aspergillus fumigatus is a major health concern in immunocompromised and
critically ill patients, manifesting as a variety of pulmonary conditions ranging from acute to chronic. In these
clinical syndromes, A. fumigatus elicits a diverse adaptive CD4 T cell response, but the mechanisms by which
these varied responses are induced remains unknown. Conventional dendritic cells (cDCs) are crucial for
sensing and initiating immune responses to this fungal pathogen and are the likely mediators of diverse T cell
responses to A. fumigatus. Recent studies have established the transcriptional basis for cDC heterogeneity
through single cell analyses, specifically demonstrating a division in the cDC2 population, which are considered
the canonical antigen presenting cells, expressing MHC Class II and priming CD4 T cells. We now separate
cDC2s into two novel subsets—cDC2A and cDC2B—based on differential expression of the transcription factors
T-bet and RORγt, respectively. In addition, the anatomic positioning of cDC2s is known to facilitate spatial
colocalization with pathogen-derived products allowing for efficient pathogen sensing, antigen uptake, and
subsequent CD4 T cell activation. Based on the pathogenic properties of A. fumigatus and recent discoveries of
cDC2 heterogeneity, our specific hypothesis is that cDC2A and cDC2B subsets will localize differently in
lung and draining lymph node and facilitate different adaptive CD4 T cell response types to A. fumigatus.
In this study, we investigate cDC2 subsets’ functionality in a clinically relevant murine model of invasive
pulmonary aspergillosis. In Specific Aim 1, we will define the temporal and spatial dynamics of cDC2 subsets
during acute A. fumigatus infection by applying high-content immunofluorescence methods and flow cytometry.
We will also assess cDC2A and cDC2B functional properties in vitro. In Specific Aim 2, we will elucidate the
direct impact of cDC2 subsets on adaptive immunity in A. fumigatus infection by implementing genetic tools to
specifically ablate cDC2A and cDC2B subsets and establish their functional significance in vivo. In addition, by
investigating spatial reorganization of other immune cell subsets in subset-specific ablation of cDC2A and
cDC2B, we can identify their significance in cellular circuits governing lung immunity. This study employs and
develops novel genetic tools, microscopy methods, and computational approaches to generate a systems level
understanding of lung immunobiology and study host-pathogen interactions. Furthermore, this proposal is
tailored for a physician-scientist in training, as it investigates the basic features of and mechanisms by which
cDC2 subsets induce adaptive immunity to the clinically relevant pathogen A. fumigatus, with implications for
anti-fungal therapeutic strategies and vaccine development.

## Key facts

- **NIH application ID:** 10141472
- **Project number:** 1F30AI154660-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Deeksha Deep
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $48,291
- **Award type:** 1
- **Project period:** 2020-12-14 → 2024-12-13

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141472

## Citation

> US National Institutes of Health, RePORTER application 10141472, Dendritic cell heterogeneity and its role in pulmonary fungal infection (1F30AI154660-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10141472. Licensed CC0.

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