Infection-induced NETosis is a dynamic process involving neutrophil multitasking in vivo

BG Yipp, B Petri, D Salina, CN Jenne, BNV Scott… - Nature medicine, 2012 - nature.com
BG Yipp, B Petri, D Salina, CN Jenne, BNV Scott, LD Zbytnuik, K Pittman, M Asaduzzaman…
Nature medicine, 2012nature.com
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 …
Abstract
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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