Tuesday, April 1, 2025 4/1/2025

The cystic fibrosis sputum compromises the ability of neutrophils to kill Staphylococcus aureus

Award Number: R21AI183057
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By:

View Award Description

The cystic fibrosis sputum compromises the ability of neutrophils to kill Staphylococcus aureus - Project summary description In cystic fibrosis (CF), lung damage is responsible for the majority of disease morbidity and mortality. While CF lungs host polymicrobial infections, lung disease has only been linked to a few bacterial pathogens including Staphylococcus aureus. S. aureus is the most prevalent infectious agent in the respiratory tract of CF patients. Neutrophil granulocytes represent the most powerful component of the healthy immune system to kill S. aureus. In CF, though, neutrophils fail to eliminate this bacterium despite their robust recruitment to the airways. It remains largely unknown why neutrophils in CF cannot eliminate S. aureus. Our published results show that the CF airway environment reduces the ability of human neutrophils to kill CF isolates of S. aureus. In contrast, the CF sputum does not affect S. aureus phagocytosis by neutrophils, extrusion of neutrophil extracellular traps or neutrophil viability. Our additional data demonstrate that CF blood neutrophils are not impaired in their abilities to kill S. aureus in vitro but the CF sputum also reduces their bactericidal activities against this bacterium. Our long-term goal is to identify why CF patients are unable to clear S. aureus from their airways. Our goal in this proposal is to determine which components of the CF sputum are responsible for its inhibitory action on neutrophils’ S. aureus killing. The rationale of the proposed work is that a deeper understanding of S. aureus pathogenesis in CF will aid to develop new, anti-staphylococcal intervention strategies for CF in the near future. Our central hypothesis is that a concerted action of IgG immune complexes and exosomes present in the CF sputum mediate the inhibitory action of CF sputum on S. aureus killing by neutrophils. Our proposed work will be expected to determine the exact component(s) of the CF sputum that compromise(s) the ability of neutrophils to kill S. aureus. This knowledge is essential for our better understanding of airway inflammation, host-pathogen interactions and S. aureus pathogenesis in CF. In addition, this exploratory work will open future studies focusing on the exact mechanism of how the CF sputum components identified here impair neutrophil functions and on exploring new, neutrophil-targeting therapies for CF.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $217,125 )
2025	2025	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	2	2/12/2025	NON-COMPETING CONTINUATION	$217,125
														Subtotal = $217,125

Issue Date FY: 2024 ( Subtotal = $186,091 )
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	001	1	9/11/2024	NEW	$18,609
2024	2024	UNIVERSITY OF GEORGIA RESEARCH FOUNDATION, INC.	310 E CAMPUS RD RM 409	ATHENS	GA	30602	CLARKE	USA	Allergy and Infectious Diseases Research	000	1	3/7/2024	NEW	$167,482
														Subtotal = $186,091

Grand Total All Awards = $403,216

Top

All Categories

About

Search

Reports

Data Submission

Award Information

The cystic fibrosis sputum compromises the ability of neutrophils to kill Staphylococcus aureus

Award Number: R21AI183057

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer