EnhancedPseudomonas aeruginosaBiofilm Development Mediated by Human Neutrophils

Abstract

Cystic fibrosis (CF) lung disease features persistent neutrophil accumulation to the airways from the time of infancy. CF children are frequently exposed to Pseudomonas aeruginosa, and by adulthood, 80% of CF patients are chronically infected. The formation of biofilms is a particularly important phenotypic characteristic of P. aeruginosa that allows for bacterial survival despite aggressive antibiotic therapy and an exuberant immune response. Here, we show that the presence of neutrophils enhances initial P. aeruginosa biofilm development over a period of 72 h through the formation of polymers comprised of actin and DNA. F-actin was found to be a site of attachment for P. aeruginosa. These actin and DNA polymers are present in CF sputum, and disruption of the polymers dispersed the associated P. aeruginosa cells and reduced biofilm development. These findings demonstrate a potential maladaptation of the primary innate response. When the host fails to eradicate the infection, cellular components from necrotic neutrophils can serve as a biological matrix to facilitate P. aeruginosa biofilm formation.

Aspergillus fumigatus Generates an Enhanced Th2-Biased Immune Response in Mice with Defective Cystic Fibrosis Transmembrane Conductance Regulator

“…Most studies addressing the mechanisms of CF airway disease pathogenesis have focused on epithelial cells and neutrophils (4,(45)(46)(47)(48)(49)(50). These cell types are important contributors to the altered airway environment.…”

Medical biofilms

“…Bacteria, on the other hand, exhibited increased oxygen consumption and detachment response that released a cloud of bacteria from the biofilm that eventually enveloped and obscured the settled neutrophils. Walker et al (2005) reports that human neutrophils serve to enhance the initial development of P. aeruginosa biofilms. The mechanism of biofilm enhancement by neutrophils was attributed to neutrophil-generated polymers comprised of actin and DNA.…”

High-dose oral N -acetylcysteine, a glutathione prodrug, modulates inflammation in cystic fibrosis

“…CF airway neutrophils are the primary source of extracellular actin (7) and DNA (8), which contribute to mucus hyperviscosity. They also release, actively or upon death, massive amounts of effector molecules, including elastase and IL-8, which perpetuate tissue damage and neutrophil recruitment and contribute to create a more favorable environment for opportunistic pathogens (9). Sputum neutrophil count and elastase activity are very strong correlates to clinical measures of CF lung dysfunction, such as declining functional expiratory volume in 1 s (FEV 1 ) or forced vital capacity (FVC) (10), which is consistent with neutrophils playing a central role in CF airway destruction.…”