title: A novel mechanism for NETosis provides antimicrobial defense at the oral mucosa.
abstract: Neutrophils are essential for host defense at the oral mucosa and neutropenia or functional neutrophil defects lead to disordered oral homeostasis. We found that neutrophils from the oral mucosa harvested from morning saliva had released neutrophil extracellular traps (undergone NETosis) in vivo. The NETosis was mediated through intracellular signals elicited by binding of sialyl Lewis(X) present on salival mucins to l-selectin on neutrophils. This led to rapid loss of nuclear membrane and intracellular release of granule proteins with subsequent neutrophil extracellular trap (NET) release independent of elastase and reduced NAD phosphate-oxidase activation. The saliva-induced NETs were more DNase-resistant and had higher capacity to bind and kill bacteria than NETs induced by bacteria or by phorbol-myristate acetate. Furthermore, saliva/sialyl Lewis(X) mediated signaling enhanced intracellular killing of bacteria by neutrophils. Saliva from patients with aphthous ulcers and Behçet disease prone to oral ulcers failed to induce NETosis, but for different reasons it demonstrated that disordered homeostasis in the oral cavity may result in deficient saliva-mediated NETosis.
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;
authors.forename: Tirthankar
authors.initials: T
authors.lastname: Mohanty
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;
authors.forename: Jonathan
authors.initials: J
authors.lastname: Sjögren
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;
authors.forename: Fredrik
authors.initials: F
authors.lastname: Kahn
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;
authors.forename: Anas H A
authors.initials: AH
authors.lastname: Abu-Humaidan
authors.affiliation: Department of Pediatrics and.
authors.forename: Niels
authors.initials: N
authors.lastname: Fisker
authors.affiliation: Department of Clinical Immunology, Odense University Hospital, Denmark;
authors.forename: Kristian
authors.initials: K
authors.lastname: Assing
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;
authors.forename: Matthias
authors.initials: M
authors.lastname: Mörgelin
authors.affiliation: Division of Rheumatology, Department of Clinical Sciences Lund, Lund University, Lund, Sweden; and.
authors.forename: Anders A
authors.initials: AA
authors.lastname: Bengtsson
authors.affiliation: The Granulocyte Research Laboratory, Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Borregaard
authors.affiliation: Division of Infection Medicine, Department of Clinical Sciences Lund, Lund University, Lund, Sweden;
authors.forename: Ole E
authors.identifier: http://orcid.org/0000-0001-8681-6921
authors.initials: OE
authors.lastname: Sørensen
mesh_terms: D000890:Anti-Infective Agents / Q000276:immunology*; D001528:Behcet Syndrome / Q000276:immunology; D002478:Cells, Cultured; D003167:Complement Activation; D065206:Extracellular Traps / Q000276:immunology*; D006801:Humans; D019041:L-Selectin / Q000276:immunology; D016256:Lewis X Antigen / Q000276:immunology; D020935:MAP Kinase Signaling System; D009061:Mouth Mucosa / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D009077:Mucins / Q000276:immunology; D019255:NADPH Oxidases / Q000276:immunology; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D012463:Saliva / Q000166:cytology / Q000276:immunology* / Q000382:microbiology; D000080506:Sialyl Lewis X Antigen
chemical_list: D000890:Anti-Infective Agents; D016256:Lewis X Antigen; D009077:Mucins; D000080506:Sialyl Lewis X Antigen; D019041:L-Selectin; D019255:NADPH Oxidases