title: Neutrophil extracellular traps downregulate lipopolysaccharide-induced activation of monocyte-derived dendritic cells.
abstract: Polymorphonuclear neutrophils (PMN) play a central role in inflammation and participate in its control, notably by modulating dendritic cell (DC) functions via soluble mediators or cell-cell contacts. Neutrophil extracellular traps (NETs) released by PMN could play a role in this context. To evaluate NET effects on DC maturation, we developed a model based on monocyte-derived DC (moDC) and calibrated NETs isolated from fresh human PMN. We found that isolated NETs alone had no discernable effect on moDC. In contrast, they downregulated LPS-induced moDC maturation, as shown by decreased surface expression of HLA-DR, CD80, CD83, and CD86, and by downregulated cytokine production (TNF-α, IL-6, IL-12, IL-23), with no increase in the expression of tolerogenic DC genes. Moreover, the presence of NETs during moDC maturation diminished the capacity of these moDC to induce T lymphocyte proliferation in both autologous and allogeneic conditions, and modulated CD4(+) T lymphocyte polarization by promoting the production of Th2 cytokines (IL-5 and IL-13) and reducing that of Th1 and Th17 cytokines (IFN-γ and IL-17). Interestingly, the expression and activities of the lymphoid chemokine receptors CCR7 and CXCR4 on moDC were not altered when moDC matured in the presence of NETs. Together, these findings reveal a new role for NETs in adaptive immune responses, modulating some moDC functions and thereby participating in the control of inflammation.
authors.affiliation: INSERM, Unité Mixte de Recherche-S 996, "Cytokines, chimiokines et immunopathologie," Université Paris-Sud, 92296 Châtenay-Malabry and Clamart, France; Université Paris-Sud, Faculté de Pharmacie, 92296 Châtenay-Malabry, France;
authors.forename: Lorena
authors.initials: L
authors.lastname: Barrientos
authors.affiliation: INSERM, Unité Mixte de Recherche-S 996, "Cytokines, chimiokines et immunopathologie," Université Paris-Sud, 92296 Châtenay-Malabry and Clamart, France; Laboratory of Excellence in Research on Medication and Innovative Therapeutics, 92296 Clamart, France;
authors.forename: Alexandre
authors.initials: A
authors.lastname: Bignon
authors.affiliation: Stallergenes, Antony Cedex 92183, France; and.
authors.forename: Claire
authors.initials: C
authors.lastname: Gueguen
authors.affiliation: INSERM, Unité Mixte de Recherche-S 996, "Cytokines, chimiokines et immunopathologie," Université Paris-Sud, 92296 Châtenay-Malabry and Clamart, France; Université Paris-Sud, Faculté de Pharmacie, 92296 Châtenay-Malabry, France; Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Paris Nord Val de Seine, Hôpital Bichat, Unité d'Immunologie (Auto-immunité et Hypersensibilités), 75018 Paris, France.
authors.forename: Luc
authors.initials: L
authors.lastname: de Chaisemartin
authors.affiliation: INSERM, Unité Mixte de Recherche-S 996, "Cytokines, chimiokines et immunopathologie," Université Paris-Sud, 92296 Châtenay-Malabry and Clamart, France; Université Paris-Sud, Faculté de Pharmacie, 92296 Châtenay-Malabry, France;
authors.forename: Roseline
authors.initials: R
authors.lastname: Gorges
authors.affiliation: INSERM, Unité Mixte de Recherche-S 996, "Cytokines, chimiokines et immunopathologie," Université Paris-Sud, 92296 Châtenay-Malabry and Clamart, France; Université Paris-Sud, Faculté de Pharmacie, 92296 Châtenay-Malabry, France;
authors.forename: Catherine
authors.initials: C
authors.lastname: Sandré
authors.affiliation: Stallergenes, Antony Cedex 92183, France; and.
authors.forename: Laurent
authors.initials: L
authors.lastname: Mascarell
authors.affiliation: INSERM, Unité Mixte de Recherche-S 996, "Cytokines, chimiokines et immunopathologie," Université Paris-Sud, 92296 Châtenay-Malabry and Clamart, France; Laboratory of Excellence in Research on Medication and Innovative Therapeutics, 92296 Clamart, France;
authors.forename: Karl
authors.initials: K
authors.lastname: Balabanian
authors.affiliation: INSERM, Unité Mixte de Recherche-S 996, "Cytokines, chimiokines et immunopathologie," Université Paris-Sud, 92296 Châtenay-Malabry and Clamart, France; Université Paris-Sud, Faculté de Pharmacie, 92296 Châtenay-Malabry, France;
authors.forename: Saadia
authors.initials: S
authors.lastname: Kerdine-Römer
authors.affiliation: INSERM, Unité Mixte de Recherche-S 996, "Cytokines, chimiokines et immunopathologie," Université Paris-Sud, 92296 Châtenay-Malabry and Clamart, France; Université Paris-Sud, Faculté de Pharmacie, 92296 Châtenay-Malabry, France;
authors.forename: Marc
authors.initials: M
authors.lastname: Pallardy
authors.affiliation: INSERM, Unité Mixte de Recherche-S 996, "Cytokines, chimiokines et immunopathologie," Université Paris-Sud, 92296 Châtenay-Malabry and Clamart, France; Université Paris-Sud, Faculté de Pharmacie, 92296 Châtenay-Malabry, France;
authors.forename: Viviana
authors.initials: V
authors.lastname: Marin-Esteban
authors.affiliation: INSERM, Unité Mixte de Recherche-S 996, "Cytokines, chimiokines et immunopathologie," Université Paris-Sud, 92296 Châtenay-Malabry and Clamart, France; Université Paris-Sud, Faculté de Pharmacie, 92296 Châtenay-Malabry, France; Assistance Publique Hôpitaux de Paris, Groupe Hospitalier Paris Nord Val de Seine, Hôpital Bichat, Unité d'Immunologie (Auto-immunité et Hypersensibilités), 75018 Paris, France sylvie.chollet-martin@u-psud.fr.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chollet-Martin
mesh_terms: D056704:Adaptive Immunity; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015536:Down-Regulation; D065206:Extracellular Traps / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D009000:Monocytes / Q000166:cytology / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D006684:HLA-DR Antigens; D018836:Inflammation Mediators; D008070:Lipopolysaccharides