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

von Köckritz-Blickwede M, Nizet V - J. Mol. Med. (2009)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of California, La Jolla, San Diego, CA 92093-0687, USA. maren@ucsd.edu

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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Related in: MedlinePlus

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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Fig2: 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

Mentions: Knowledge is beginning to emerge regarding the cellular processes that precede the formation of NETs by activated neutrophils (summarized in Fig. 2). Evidence implicates the production of ROS such as superoxide (O2−) or H2O2 as an essential signal leading to the induction of unique cell death program and the elaboration of NETs [4]. Interference with ROS generation using diphenylene iodonium (DPI), an inhibitor of NADPH oxidase enzymes, blocks the formation of NETs. This process is morphologically distinct from other classical cell death processes including apoptosis and necrosis and hence was dubbed “NETosis” [15]. One key biochemical marker of NET formation appears to be the deimination of arginine residues in histones to citrullines, a posttranslational modification catalyzed by peptidyl arginine deaminase that aids in chromatin decondensation. Hypercitrullinated histones were detected in NETs released by neutrophils activated by LPS and H2O2 but not in neutrophils treated with staurosporine or camptothecin to induce apoptosis [16, 17].Fig. 2


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

von Köckritz-Blickwede M, Nizet V - J. Mol. Med. (2009)

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
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2707954&req=5

Fig2: 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
Mentions: Knowledge is beginning to emerge regarding the cellular processes that precede the formation of NETs by activated neutrophils (summarized in Fig. 2). Evidence implicates the production of ROS such as superoxide (O2−) or H2O2 as an essential signal leading to the induction of unique cell death program and the elaboration of NETs [4]. Interference with ROS generation using diphenylene iodonium (DPI), an inhibitor of NADPH oxidase enzymes, blocks the formation of NETs. This process is morphologically distinct from other classical cell death processes including apoptosis and necrosis and hence was dubbed “NETosis” [15]. One key biochemical marker of NET formation appears to be the deimination of arginine residues in histones to citrullines, a posttranslational modification catalyzed by peptidyl arginine deaminase that aids in chromatin decondensation. Hypercitrullinated histones were detected in NETs released by neutrophils activated by LPS and H2O2 but not in neutrophils treated with staurosporine or camptothecin to induce apoptosis [16, 17].Fig. 2

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, University of California, La Jolla, San Diego, CA 92093-0687, USA. maren@ucsd.edu

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.

Show MeSH
Related in: MedlinePlus