The Journal of Immunology · 2012 · 317 citations · 38 references
Life SciencesCell BiologyImmunologyAdaptive ImmunityInflammationInnate ImmunityInflammatory Cell ResponsesInnate Immune ActivationInnate Immune ResponseNeutrophil BiologyPhagocyte BiologyT Cell BiologyInflammatory T Cell ResponsesInnate Immune EffectorsInnate Immune ProtectionInnate Immunity PathwaysNeutrophil Effector FunctionsNeutrophil PhysiologyNeutrophil-mediated InflammationPlasmacytoid Dendritic Cell Responses
Polymorphonuclear neutrophils defend against infections by releasing neutrophil extracellular traps (NETs), chromatin fibers with antimicrobial proteins that trap and kill pathogens while modulating inflammation. The study demonstrates that NETs directly prime T cells by lowering their activation threshold, enhancing responses to antigens and suboptimal stimuli through cell contact and TCR signaling, independently of TLR9.
Abstract Polymorphonuclear neutrophils constitute the first line of defense against infections. Among their strategies to eliminate pathogens they release neutrophil extracellular traps (NETs), being chromatin fibers decorated with antimicrobial proteins. NETs trap and kill pathogens very efficiently, thereby minimizing tissue damage. Furthermore, NETs modulate inflammatory responses by activating plasmacytoid dendritic cells. In this study, we show that NETs released by human neutrophils can directly prime T cells by reducing their activation threshold. NETs-mediated priming increases T cell responses to specific Ags and even to suboptimal stimuli, which would not induce a response in resting T cells. T cell priming mediated by NETs requires NETs/cell contact and TCR signaling, but unexpectedly we could not demonstrate a role of TLR9 in this mechanism. NETs-mediated T cell activation adds to the list of neutrophil functions and demonstrates a novel link between innate and adaptive immune responses.
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