title: Signal Inhibitory Receptor on Leukocytes-1 Limits the Formation of Neutrophil Extracellular Traps, but Preserves Intracellular Bacterial Killing.
abstract: In response to microbial invasion, neutrophils release neutrophil extracellular traps (NETs) to trap and kill extracellular microbes. Alternatively, NET formation can result in tissue damage in inflammatory conditions and may perpetuate autoimmune disease. Intervention strategies that are aimed at modifying pathogenic NET formation should ideally preserve other neutrophil antimicrobial functions. We now show that signal inhibitory receptor on leukocytes-1 (SIRL-1) attenuates NET release by human neutrophils in response to distinct triggers, including opsonized Staphylococcus aureus and inflammatory danger signals. NET release has different kinetics depending on the stimulus, and rapid NET formation is independent of NADPH oxidase activity. In line with this, we show that NET release and reactive oxygen species production upon challenge with opsonized S. aureus require different signaling events. Importantly, engagement of SIRL-1 does not affect bacterially induced production of reactive oxygen species, and intracellular bacterial killing by neutrophils remains intact. Thus, our studies define SIRL-1 as an intervention point of benefit to suppress NET formation in disease while preserving intracellular antimicrobial defense.
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, 3584 EA Utrecht, the Netherlands;
authors.forename: Kristof
authors.initials: K
authors.lastname: Van Avondt
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, 3584 EA Utrecht, the Netherlands;
authors.forename: Maarten
authors.initials: M
authors.lastname: van der Linden
authors.affiliation: Department of Microbiology-Infectiology and Immunology, Faculty of Medicine, Laval University, Quebec, Quebec G1V 4G2, Canada; and.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Naccache
authors.affiliation: Cell Screening Core, Center for Molecular Medicine, Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, the Netherlands.
authors.forename: David A
authors.initials: DA
authors.lastname: Egan
authors.affiliation: Laboratory of Translational Immunology, Department of Immunology, University Medical Center Utrecht, 3584 EA Utrecht, the Netherlands; l.meyaard@umcutrecht.nl.
authors.forename: Linde
authors.initials: L
authors.lastname: Meyaard
mesh_terms: D003593:Cytoplasm / Q000382:microbiology*; D065206:Extracellular Traps / Q000276:immunology / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D007700:Kinetics; D019255:NADPH Oxidases / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology* / Q000382:microbiology; D010587:Phagocytosis; D017382:Reactive Oxygen Species / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology*; D015398:Signal Transduction; D013211:Staphylococcus aureus / Q000276:immunology* / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D011971:Receptors, Immunologic; C550469:VSTM1 protein, human; D019255:NADPH Oxidases