title: TLR-Stimulated Neutrophils Instruct NK Cells To Trigger Dendritic Cell Maturation and Promote Adaptive T Cell Responses.
abstract: Polymorphonuclear neutrophils (PMNs) are innate effector cells with pivotal roles in pathogen recognition, phagocytosis, and eradication. However, their role in the development of subsequent immune responses is incompletely understood. This study aimed to identify mechanisms of relevance to the cross talk between human neutrophils and NK cells and its potential role in promoting adaptive immunity. TLR-stimulated PMNs were found to release soluble mediators to attract and activate NK cells in vitro. PMN-conditioned NK cells displayed enhanced cytotoxicity and cytokine production, and responded vigorously to ensuing stimulation with exogenous and endogenous IL-12. The neutrophil-induced activation of NK cells was prevented by caspase-1 inhibitors and by natural antagonists to IL-1 and IL-18, suggesting a role for the NOD-like receptor family pyrin domain containing-3 inflammasome. In addition, PMN-conditioned NK cells triggered the maturation of monocyte-derived dendritic cells, which promoted T cell proliferation and IFN-γ production. These data imply that neutrophils attract NK cells to sites of infection to convert these cells into an active state, which drives adaptive immune responses via maturation of dendritic cells. Our results add to a growing body of evidence that suggests a sophisticated role for neutrophils in orchestrating the immune response to pathogens.
authors.affiliation: Sahlgrenska Cancer Center, University of Gothenburg, 40530 Gothenburg, Sweden;
authors.forename: Rebecca E
authors.initials: RE
authors.lastname: Riise
authors.affiliation: Sahlgrenska Cancer Center, University of Gothenburg, 40530 Gothenburg, Sweden;
authors.forename: Elin
authors.initials: E
authors.lastname: Bernson
authors.affiliation: Sahlgrenska Cancer Center, University of Gothenburg, 40530 Gothenburg, Sweden;
authors.forename: Johan
authors.initials: J
authors.lastname: Aurelius
authors.affiliation: Sahlgrenska Cancer Center, University of Gothenburg, 40530 Gothenburg, Sweden;
authors.forename: Anna
authors.initials: A
authors.lastname: Martner
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genoa, Italy;
authors.forename: Silvia
authors.initials: S
authors.lastname: Pesce
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genoa, Italy;
authors.forename: Mariella
authors.initials: M
authors.lastname: Della Chiesa
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genoa, Italy; Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, 16132 Genoa, Italy;
authors.forename: Emanuela
authors.initials: E
authors.lastname: Marcenaro
authors.affiliation: Department of Oral Microbiology and Immunology, University of Gothenburg, 40530 Gothenburg, Sweden; and.
authors.forename: Johan
authors.initials: J
authors.lastname: Bylund
authors.affiliation: Sahlgrenska Cancer Center, University of Gothenburg, 40530 Gothenburg, Sweden;
authors.forename: Kristoffer
authors.initials: K
authors.lastname: Hellstrand
authors.affiliation: Istituto Giannina Gaslini, 16147 Genoa, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Moretta
authors.affiliation: Dipartimento di Medicina Sperimentale, Università di Genova, 16132 Genoa, Italy; Centro di Eccellenza per la Ricerca Biomedica, Università di Genova, 16132 Genoa, Italy;
authors.forename: Alessandro
authors.initials: A
authors.lastname: Moretta
authors.affiliation: Sahlgrenska Cancer Center, University of Gothenburg, 40530 Gothenburg, Sweden; fredrik.thoren@gu.se.
authors.forename: Fredrik B
authors.initials: FB
authors.lastname: Thorén
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D002352:Carrier Proteins / Q000276:immunology; D020170:Caspase 1 / Q000378:metabolism; D061945:Caspase Inhibitors / Q000494:pharmacology; D002450:Cell Communication / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology; D006801:Humans; D058847:Inflammasomes / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D053765:Interleukin-12 Subunit p35 / Q000276:immunology; D020382:Interleukin-18 / Q000037:antagonists & inhibitors; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009504:Neutrophils / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D002352:Carrier Proteins; D061945:Caspase Inhibitors; C508858:IL12A protein, human; D058847:Inflammasomes; D053765:Interleukin-12 Subunit p35; D020382:Interleukin-18; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D007371:Interferon-gamma; D020170:Caspase 1