The last decade has witnessed the delineation of innate immunity - a new area which has revolutionized our understanding of host-parasite interactions and their impact on defense mechanisms in infectious and noninfectious diseases. This volume of the book series 'Contributions to Microbiology' provides an update of the current knowledge of this expanding field of research and highlights some of its most important aspects. In eleven state-of-the-art articles, eminent international experts in the field address topics such as the innate immune system in mammals and insects, microbial protein ligands, antimicrobial peptides, complement, antibacterial chemokines, the role of neutrophils and monocytes, oxidative innate immune defenses and the effect of aging on innate immunity. The book will be a valuable resource for microbiologists, immunologists, students, scientists of other related disciplines, and clinicians with an interest in infectious or immunological diseases.
164 - 187: Oxidative Innate Immune Defenses by Nox/Duox Family NADPH Oxidases
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Published:2008
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Book Series: Contributions to Microbiology
Balázs Rada, Thomas L. Leto, 2008. "Oxidative Innate Immune Defenses by Nox/Duox Family NADPH Oxidases", Trends in Innate Immunity, H. Herwald, A. Schmidt, A. Egesten
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Abstract
The importance of reactive oxygen species (ROS) in innate immunity was first recognized in professionalphagocytes undergoing a ‘respiratory burst’upon activation. This robust oxygen consumption is related to asuperoxide-generating enzyme, the phagocytic NADPH oxidase (Nox2-based or phox). The oxidase is essentialfor microbial killing, since patients lacking a functional oxidase suffer from enhanced susceptibility to microbialinfections. ROS derived from superoxide attack bacteria in the isolated niche of the neutrophil phagosome.The oxidase is electrogenic, alters ion currents across membranes, induces apoptosis, regulatescytokine production, influences gene expression, and promotes formation of extracellular traps. Recently,new homologues of Nox2 were discovered establishing the Nox family of NADPH oxidases that encompassesseven members. Nox1 is highly expressed in the colon epithelium, and can be induced by LPS or IFN-ϒ. Nox4 was implicated in innate immunity since LPS induces Nox4-dependent ROS generation. Duox1 andDuox2 localize to the apical plasma membrane of epithelial cells in major airways, salivary glands, and thegastrointestinal tract, and provide extracellular hydrogen peroxide to lactoperoxidase to produce antimicrobialhypothiocyanite ions. Th1 and Th2 cytokines regulate expression of dual oxidases in human airways andmay thereby act in host defense or in proinflammatory responses.
