Abstract
Neutrophil extracellular traps (NETs), a web-like structures containing chromatin, have a significant role in assisting the capture and killing of microorganisms by neutrophils during infection. The specific engagement of cell-surface receptors by extracellular signaling molecules activates diverse intracellular signaling cascades and regulates neutrophil effector functions, including phagocytosis, reactive oxygen species release, degranulation, and NET formation. However, overproduction of NETs is closely related to the occurrence of inflammation, autoimmune disorders, non-canonical thrombosis and tumor metastasis. Therefore, it is necessary to understand neutrophil activation signals and the subsequent formation of NETs, as well as the related immune regulation. In this review, we provide an overview of the immunoreceptor-mediated regulation of NETosis. The pathways involved in the release of NETs during infection or stimulation by noninfectious substances are discussed in detail. The mechanisms by which neutrophils undergo NETosis help to refine our views on the roles of NETs in immune protection and autoimmune diseases, providing a theoretical basis for research on the immune regulation of NETs.
Highlights
Faced with daily exposure to various pathogens, humans rely heavily on the innate immune system as a first responder to intruders
In contrast to the relatively slow suicidal NETosis pathway, vital NETosis involves the rapid release of neutrophil extracellular traps (NETs) stimulated by microorganisms, activated platelets (PLTs), or complement proteins through neutrophil surface receptors, which appears to be independent of NOX activity [20, 21]
The results presented for neutrophils in contact with opsonized S. aureus or hypervirulent Klebsiella pneumoniae suggested that activation of Fc receptors (FcRs) could enhance the release of NETs [54, 66]
Summary
Faced with daily exposure to various pathogens, humans rely heavily on the innate immune system as a first responder to intruders. In contrast to the relatively slow suicidal NETosis pathway, vital NETosis involves the rapid release of NETs stimulated by microorganisms, activated platelets (PLTs), or complement proteins through neutrophil surface receptors, which appears to be independent of NOX activity [20, 21]. In this pathway, the main feature of vital NETosis is activation by Ca2+-activated PAD4, citrullinating H3 and participating DNA decondensation with the cooperation of MPO and NE [22]. It is still controversial whether mitoROS are involved in NOX-independent NETosis
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