Redox warfare between airway epithelial cells and Pseudomonas: dual oxidase versus pyocyanin
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Redox warfare between airway epithelial cells and Pseudomonas: dual oxidase versus pyocyanin Balázs Rada · Thomas L. Leto
Published online: 1 November 2008 © Humana Press Inc. 2008
Abstract The importance of reactive oxygen species-dependent microbial killing by the phagocytic cell NADPH oxidase has been appreciated for some time, although only recently has an appreciation developed for the partnership of lactoperoxidase with related dual oxidases (Duox) within secretions of the airway surface layer. This system produces mild oxidants designed for extracellular killing that are eVective against several airway pathogens, including Staphylococcus aureus, Burkholderia cepacia, and Pseudomonas aeruginosa. Establishment of chronic pseudomonas infections involves adaptations to resist oxidant-dependent killing by expression of a redox-active virulence factor, pyocyanin, that competitively inhibits epithelial Duox activity by consuming intracellular NADPH and producing superoxide, thereby inXicting oxidative stress on the host. Keywords NADPH oxidase · Nox · Dual oxidase · Pyocyanin · Pseudomonas aeruginosa · Cystic Wbrosis · Airway epithelium · Hydrogen peroxide · Oxidative stress
Introduction Circulating phagocytic blood cells exhibit a remarkable capacity for generating large amounts of reactive oxygen species (ROS) during the engulfment of microbial pathogens, a process referred to as the “respiratory burst” [1]. This activity is attributed to oxygen consumption by the phagocytic NADPH oxidase (phox) complex, an enzyme that donates electrons from NADPH to molecular oxygen to generate superoxide anion, a short-lived precursor of other potent antimicrobial oxidants (hydrogen peroxide (H2O2) and hypochlorous acid) usually produced within the conWnes of phagosomes. Oxidant-dependent microbial killing by circulating phagocytes has been recognized as an essential component of innate immunity; defects in any one of four genes encoding phagocytic oxidase components
B. Rada · T. L. Leto (&) Laboratory of Host Defenses, National Institutes of Health, National Institute of Allergy and Infectious Diseases, 12441 Parklawn Drive, 20852 Rockville, MD, USA e-mail: [email protected]
Immunol Res (2009) 43:198–209
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result in chronic granulomatous disease (CGD), a hereditary immune deWciency characterized by enhanced susceptibility to low-grade bacterial and fungal pathogens and dysregulated inXammatory responses [2]. More than a decade ago, investigators began to appreciate that deliberate ROS production by the host is not limited to phagocytic cells, and that even low levels of ROS production serve a variety of essential functions, including redox-based cell signaling, vascular regulation, hormone biosynthesis, extracellular matrix cross-linking, oxygen sensing, and alterations in gene expression in response to redox signals [3]. At the same time that these novel roles for ROS were being described, the rapid expansion of genome sequence databases led investigators to realize that the phagocytic NADPH oxidase is but one member of a
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