# Heterogeneous immune responses of the alveolar macrophage population during pulmonary fungal infections

> **NIH NIH R01** · DUKE UNIVERSITY · 2021 · $517,836

## Abstract

PROJECT SUMMARY/ABSTRACT
 Alveolar macrophages (AMs) are lung-resident macrophages. They are one of the cell types that first
encounter inhaled fungal pathogens. Currently, the role of AMs in fungal infections is still elusive; some articles
reported AMs to be protective, but others showed them detrimental. The challenge to study AMs is that
identification and evaluation of AMs in vivo require technologies such as; multi-color flow cytometry, reporter and
fate-mapping (FM) mouse systems, and single cell-level of gene expression analyses. By using these
technologies, we will elucidate the biological functions of AMs during pulmonary fungal infections.
 We recently demonstrated that AMs are the bona fide immune sentinels that respond to fungal infections
and also elicit heterogeneous immune responses. In particular, fungal infections generate pro- and anti-
inflammatory AM subpopulations simultaneously, and AM subpopulations with distinct functions co-exist in the
infected lung. Such heterogeneity within the AM population cannot be elicited by pulmonary instillation of Toll-
like recent ligands, suggesting possible specificity in fungal infections, likely through C-tyle lectin receptor
signaling.
 The central hypothesis of this proposed study is: AMs develop into pro- and anti-inflammatory AMs in
vivo at the level of transcriptional and epigenetic regulations, respectively. The generation of AM subpopulations
with dichotomous functions is considered to maximize fungal clearance and minimize collateral damage in the
lung. The objective of this proposed study is to identify the biological implication of functionally distinct AM
subpopulations and to elucidate the detailed molecular mechanism by which the heterogeneous AM
subpopulations are generated, maintained, and lost during fungal infections in vivo.

## Key facts

- **NIH application ID:** 10387058
- **Project number:** 1R01AI160737-01A1
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Mari L. Shinohara
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $517,836
- **Award type:** 1
- **Project period:** 2021-09-24 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10387058

## Citation

> US National Institutes of Health, RePORTER application 10387058, Heterogeneous immune responses of the alveolar macrophage population during pulmonary fungal infections (1R01AI160737-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10387058. Licensed CC0.

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