title: T lymphocyte priming by neutrophil extracellular traps links innate and adaptive immune responses.
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.
authors.affiliation: Institute for Neuroimmunology and Clinical Multiple Sclerosis Research, Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany.
authors.forename: Kati
authors.initials: K
authors.lastname: Tillack
authors.forename: Petra
authors.initials: P
authors.lastname: Breiden
authors.forename: Roland
authors.initials: R
authors.lastname: Martin
authors.forename: Mireia
authors.initials: M
authors.lastname: Sospedra
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002450:Cell Communication; D002455:Cell Division; D002478:Cells, Cultured / Q000276:immunology / Q000648:ultrastructure; D002843:Chromatin / Q000276:immunology; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology; D005110:Extracellular Space / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000235:genetics; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000235:genetics; D039841:Leukocyte L1 Antigen Complex / Q000276:immunology; D009504:Neutrophils / Q000276:immunology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051217:Toll-Like Receptor 9 / Q000037:antagonists & inhibitors / Q000502:physiology; D015854:Up-Regulation; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000378:metabolism; D000099192:CD69 Antigens
chemical_list: D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002843:Chromatin; D016207:Cytokines; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D039841:Leukocyte L1 Antigen Complex; D051217:Toll-Like Receptor 9; D051746:ZAP-70 Protein-Tyrosine Kinase; D000099192:CD69 Antigens; C508017:IL2RA protein, human; C495371:TLR9 protein, human; C497261:ZAP70 protein, human