# Neutrophil Nox2 controls mononuclear cell functions in inflammation; role in CGD

> **NIH NIH R01** · NATIONAL JEWISH HEALTH · 2020 · $622,760

## Abstract

Project Summary / Abstract
Chronic granulomatous disease (CGD) is a rare, but devastating, disease with known genetic abnormalities in
the phagocyte (white blood cell) oxidase. In addition to immunodeficiency (the inability to fight certain bacteria
and fungi), patients with this disease often have complex and poorly understood abnormalities in inflammatory
processes manifest as colitis, poor wound healing, obstructing granuloma, and autoimmunity. Importantly,
there is a lack of clearly applicable and effective treatments for many of these inflammatory consequences.
Our studies in an animal model of human X-linked CGD clearly point to abnormal crosstalk during inflammatory
processes between two different types of phagocytes, both with the mutated oxidase: neutrophils (or
granulocytes) and mononuclear phagocytes. Specifically, we have shown that whereas CGD neutrophils were
unable control the recruitment, maturation, inflammatory programming and disposal of the mononuclear
phagocytes at sites of inflammation, the direct introduction of normal neutrophils was able to restore these
activities and events in vivo. As such, signals from normal neutrophils orchestrate the activities of the
mononuclear phagocytes at each step in the normal development and resolution of inflammation. It is
hypothesized that identifying these signals provided by normal neutrophils could provide new therapeutic
strategies. Using the murine model and adoptive transfers of neutrophils and their products as well as cell co-
culture experiments (ex vivo), this proposal aims to define the mechanisms underlying the abnormal
mononuclear phagocyte behavior in CGD and the precise processes lacking in CGD neutrophils that are
overcome by the addition of normal neutrophils. Defining these is expected to lead to novel approaches to
treatment of CGD and possibly other chronic inflammatory conditions.
.

## Key facts

- **NIH application ID:** 9986683
- **Project number:** 5R01AI141389-03
- **Recipient organization:** NATIONAL JEWISH HEALTH
- **Principal Investigator:** DONNA L BRATTON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $622,760
- **Award type:** 5
- **Project period:** 2018-09-18 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9986683

## Citation

> US National Institutes of Health, RePORTER application 9986683, Neutrophil Nox2 controls mononuclear cell functions in inflammation; role in CGD (5R01AI141389-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9986683. Licensed CC0.

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