Comprehensive Analysis of The Interactions between Pseudomonas aeruginosa and Neutrophils in Cystic Fibrosis

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University of Guelph

Abstract

Cystic fibrosis (CF) is characterized by chronic inflammation and persistent microbial infections. As a first line of defense against infections, the host’s immune system will recruit neutrophils; however, in CF patients, mutations within the cystic fibrosis transmembrane receptor (e.g., ΔF508) render neutrophils ineffective at clearing infections. Notably, CF-associated neutrophils demonstrate impaired effector function compared to wild-type (WT) neutrophils, causing altered antimicrobial protein/enzyme production. To identify key drivers of neutrophilic differences, I assessed biofilm disruption and microbial survival between the cell lines. Additionally, to define protein level differences in CF vs WT neutrophils, this study used quantitative proteomics to identify core and unique proteome signatures between the cell lines and infection models. Here, we identified many neutrophil proteins with significantly altered abundance across the conditions, including bactericidal permeability-increasing protein and cathepsin G, elevated in P. aeruginosa-exposed WT neutrophils. Together, this work will enhance our understanding of CF-associated neutrophil regulatory mechanisms during P. aeruginosa biofilm infection, supporting the putative discovery of novel therapeutic strategies to clear bacterial infections.

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Cystic Fibrosis, Neutrophils, Proteomics

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