Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo
Bacteria can be trapped by neutrophil extracellular traps (NETs) in vitro , but their relevance in vivo is uncertain, in part because NETs are thought to be released by dying neutrophils, thereby eliminating the other antimicrobial functions of these cells. Paul Kubes and his colleagues report in th...
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Veröffentlicht in: | Nature medicine 2012-09, Vol.18 (9), p.1386-1393 |
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Sprache: | eng |
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Zusammenfassung: | Bacteria can be trapped by neutrophil extracellular traps (NETs)
in vitro
, but their relevance
in vivo
is uncertain, in part because NETs are thought to be released by dying neutrophils, thereby eliminating the other antimicrobial functions of these cells. Paul Kubes and his colleagues report in this issue that NET release need not kill neutrophils and that NETosis can by dynamically imaged
in vivo
.
Neutrophil extracellular traps (NETs) are released as neutrophils die
in vitro
in a process requiring hours, leaving a temporal gap that invasive microbes may exploit. Neutrophils capable of migration and phagocytosis while undergoing NETosis have not been documented. During Gram-positive skin infections, we directly visualized live polymorphonuclear cells (PMNs)
in vivo
rapidly releasing NETs, which prevented systemic bacterial dissemination. NETosis occurred during crawling, thereby casting large areas of NETs. NET-releasing PMNs developed diffuse decondensed nuclei, ultimately becoming devoid of DNA. Cells with abnormal nuclei showed unusual crawling behavior highlighted by erratic pseudopods and hyperpolarization consistent with the nucleus being a fulcrum for crawling. A requirement for both Toll-like receptor 2 and complement-mediated opsonization tightly regulated NET release. Additionally, live human PMNs injected into mouse skin developed decondensed nuclei and formed NETS
in vivo
, and intact anuclear neutrophils were abundant in Gram-positive human abscesses. Therefore early in infection NETosis involves neutrophils that do not undergo lysis and retain the ability to multitask. |
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ISSN: | 1078-8956 1546-170X |
DOI: | 10.1038/nm.2847 |