# Regulation of dendritic cell function by neutrophil-derived reactive oxygen species in pulmonary aspergillosis

> **NIH NIH K08** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $165,024

## Abstract

PROJECT SUMMARY/ABSTRACT
This proposal outlines a five-year training program for Dr. Cagnina to establish a career as an independent
investigator in Pulmonary and Critical Care Medicine. Under the guidance of co-mentors Drs. Borna Mehrad
and Tom Braciale, our broad, long-term objective is for Dr. Cagnina to gain new the knowledge and skills
necessary to evolve into an independent physician-scientist, while making significant contributions to
understanding the immune response to Aspergillus. Aspergillus species are ubiquitous molds that cause
clinical disease in hosts with impaired immunity or abnormal mucosal defenses. Neutrophils play a key role in
host defenses against this pathogen but little is known about the contribution of these cells in in this context
beyond their direct microbicidal role. We have previously shown that, during host response to Aspergillus in the
lung, neutropenia results in a defect in the traffic and maturation of inflammatory monocyte-derived dendritic
cells. In the preliminary data for this proposal, we report that deficiency in neutrophil reactive oxygen species
production is sufficient to induce this phenotype; that, in hosts unable to generate reactive oxygen species,
both the inflammatory dendritic cell recruitment and lung injury are dependent on TNF; and that neutropenia
impairs the development of protective immunity against the pathogen. We therefore seek to test the
hypothesis that in response to Aspergillus, reactive oxygen species-dependent neutrophil signaling to
inflammatory dendritic cells mediates (a) protection from acute lung injury and (b) generation of protective
adaptive immunity against Aspergillus. We will test this under two specific aims: (1) To identify the
mechanism by which neutrophil-derived ROS modulates dendritic cell function during the innate immune
response to Aspergillus and (2) To define the role of neutrophil ROS in the development of protective adaptive
immunity against Aspergillus. The proposed studies are relevant to public health by defining a new
mechanism of host defense against an important human pathogen that should allow for future development of
novel therapeutics or preventative strategies.

## Key facts

- **NIH application ID:** 10162640
- **Project number:** 5K08HL136903-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Rebecca Elaine Cagnina
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $165,024
- **Award type:** 5
- **Project period:** 2017-05-03 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10162640

## Citation

> US National Institutes of Health, RePORTER application 10162640, Regulation of dendritic cell function by neutrophil-derived reactive oxygen species in pulmonary aspergillosis (5K08HL136903-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10162640. Licensed CC0.

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