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Review
. 2009 Aug;87(8):775-83.
doi: 10.1007/s00109-009-0481-0. Epub 2009 May 16.

Innate immunity turned inside-out: antimicrobial defense by phagocyte extracellular traps

Affiliations
Review

Innate immunity turned inside-out: antimicrobial defense by phagocyte extracellular traps

Maren von Köckritz-Blickwede et al. J Mol Med (Berl). 2009 Aug.

Abstract

The formation of extracellular traps (ETs) by phagocytic cells has been recognized as a novel and important mechanism of the host innate immune response against infections. ETs are formed by different host immune cells such as neutrophils, mast cells, and eosinophils after stimulation with mitogens, cytokines, or pathogens themselves, in a process dependent upon induction of a reactive-oxygen-species-mediated signaling cascade. ETs consist of nuclear or mitochondrial DNA as a backbone with embedded antimicrobial peptides, histones, and cell-specific proteases and thereby provide a matrix to entrap and kill microbes and to induce the contact system. This review summarizes the latest research on ETs and their role in innate immunity and host innate defense. Attention is also given to mechanisms by which certain leading bacterial pathogens have evolved to avoid entrapment and killing in these specialized structures.

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Figures

Fig. 1
Fig. 1
Bacterial entrapment in NETs: three-dimensional confocal micrograph of FITC-labeled S. aureus (strain Cowan) entrapped by human neutrophil extracellular traps, as visualized by the blue DNA dye DAPI
Fig. 2
Fig. 2
Model for formation of neutrophil extracellular traps. Neutrophils are activated by contact with microbial pathogens different stimuli such as LPS, IL-8, PMA, IFN-α/γ + C5a or GM-CSF + C5a. Stimulation of neutrophils results in the activation of NADPH oxidases and the formation of reactive oxygen species (ROS). ROS signaling is required for the novel cell death pathway of ETosis, which is characterized by the disruption of the nuclear membrane, chromatin decondensation, and the mixing of nuclear contents with cytoplasmic and granular proteins. As a final step, nuclear and granular components are released by the dead cell generating the extracellular traps. Extracellular traps have the ability to entrap and/or kill different microbes, while also enhancing proinflammatory innate immune responses

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