# Myeloid CFTR Defect and CF Pathogen Selection

> **NIH NIH R21** · LSU HEALTH SCIENCES CENTER · 2020 · $183,750

## Abstract

ABSTRACT
 Cystic fibrosis (CF), one of the most common genetic disorders, is caused by mutations in the CF
transmembrane conductance regulator (CFTR) gene that encodes a cAMP-activated chloride channel.
Clinically, over 90% of CF patients die of lung bacterial infection. Despite great progress made in
understanding the molecular defect of this disease, the central issue as to how the chloride channel defect
leads to the host lung defense failure has not been solved. CF lung infections are surprisingly restricted to a
narrow set of opportunistic pathogens, including Pseudomonas aeruginosa, Staphylococcus aureus and
Haemophilus influenzae. It is unknown why CF lungs selectively permit the prevalence of these particular
bacteria. In normal host lung defense, neutrophils and monocytes/macrophages are the two major lung-
recruited immune cells utilized against lung bacterial infection. We previously discovered that CFTR
dysfunction in CF neutrophils undermines their capacity to kill Pseudomonas aeruginosa. Research from other
laboratories identified a similar defect in CF macrophages. However, whether these innate immune defects
determine CF lung pathogen selection has not been investigated. We hypothesize that myeloid CFTR defect in
lung-recruited immune cells disproportionately affects the killing of CF pathogens versus non-CF pathogens,
giving the CF pathogens a survival advantage. To test this hypothesis, we put forward two specific aims for this
R21 proposal: 1) to verify that CFTR loss-of-function in neutrophils and/or monocytes/macrophages affects
lung bacterial clearance disproportionately in favor of CF pathogens; 2) to test that adoptive transfer of
functional neutrophils or monocytes corrects the CF pathogen clearance defect differentially. Completion of this
research will demonstrate the central role of CF innate immune cells in CF lung disease pathogenesis, which
may reveal novel therapeutic targets for the development of effective therapies for CF, a devastating disease
that affects 1/~3000 live births in the US.

## Key facts

- **NIH application ID:** 9843972
- **Project number:** 5R21AI140088-02
- **Recipient organization:** LSU HEALTH SCIENCES CENTER
- **Principal Investigator:** GUOSHUN WANG
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $183,750
- **Award type:** 5
- **Project period:** 2019-01-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9843972

## Citation

> US National Institutes of Health, RePORTER application 9843972, Myeloid CFTR Defect and CF Pathogen Selection (5R21AI140088-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9843972. Licensed CC0.

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