title: Neutrophils can disarm NK cell response through cleavage of NKp46.
abstract: Polymorphonuclear neutrophils (PMNs) can contribute to the regulation of the host immune response by crosstalk with innate and adaptive leukocytes, including NK cells. Mechanisms by which this immunoregulation process occurs remain incompletely understood. Here, we focused on the effect of human neutrophil-derived serine proteases on NKp46, a crucial activating receptor expressed on NK cells. We used flow cytometry, Western blotting, and mass spectrometry (MS) analysis to reveal that cathepsin G [CG; and not elastase or proteinase 3 (PR3)] induces a time- and concentration-dependent, down-regulatory effect on NKp46 expression through a restricted proteolytic mechanism. We also used a functional assay to demonstrate that NKp46 cleavage by CG severely impairs NKp46-mediated responses of NK cells, including IFN-γ production and cell degranulation. Importantly, sputa of cystic fibrosis (CF) patients, which have high concentrations of CG, also alter NKp46 on NK cells. Hence, we have identified a new immunoregulatory mechanism of neutrophils that proteolytically disarms NK cell responses.
authors: Université François Rabelais de Tours, Tours, France.|Institut National de la Santé et de la Recherche Médicale, Centre d'Etude des Pathologies Respiratoires, Unite Mixte de Recherche 1100, Tours, France.
authors: Alexandre
authors: A
authors: Valayer
authors: Université François Rabelais de Tours, Tours, France.|Institut National de la Santé et de la Recherche Médicale, Centre d'Etude des Pathologies Respiratoires, Unite Mixte de Recherche 1100, Tours, France.
authors: Deborah
authors: D
authors: Brea
authors: Université François Rabelais de Tours, Tours, France.|Centre National de la Recherche Scientifique Génétique, Immunothérapie, Chimie et Cancer, Unite Mixte de Recherche 7292, Centre Hospitalier Régional et Universitaire de Tours, France; and.
authors: Laurie
authors: L
authors: Lajoie
authors: Université François Rabelais de Tours, Tours, France.|Institut National de la Santé et de la Recherche Médicale, Centre d'Etude des Pathologies Respiratoires, Unite Mixte de Recherche 1100, Tours, France.
authors: Leslie
authors: L
authors: Avezard
authors: Institut National de la Recherche Agronomique, Plateforme d'Analyse Intégrative des Biomolécules, Unite Mixte de Recherche 85, Laboratoire de Spectrométrie de Masse, Nouzilly, France.
authors: Lucie
authors: L
authors: Combes-Soia
authors: Institut National de la Recherche Agronomique, Plateforme d'Analyse Intégrative des Biomolécules, Unite Mixte de Recherche 85, Laboratoire de Spectrométrie de Masse, Nouzilly, France.
authors: Valerie
authors: V
authors: Labas
authors: Université François Rabelais de Tours, Tours, France.|Institut National de la Santé et de la Recherche Médicale, Centre d'Etude des Pathologies Respiratoires, Unite Mixte de Recherche 1100, Tours, France.
authors: Brice
authors: B
authors: Korkmaz
authors: Université François Rabelais de Tours, Tours, France.|Centre National de la Recherche Scientifique Génétique, Immunothérapie, Chimie et Cancer, Unite Mixte de Recherche 7292, Centre Hospitalier Régional et Universitaire de Tours, France; and.
authors: Gilles
authors: G
authors: Thibault
authors: Université François Rabelais de Tours, Tours, France; baranek@univ-tours.fr.|Institut National de la Santé et de la Recherche Médicale, Centre d'Etude des Pathologies Respiratoires, Unite Mixte de Recherche 1100, Tours, France.
authors: Thomas
authors: T
authors: Baranek
authors: Université François Rabelais de Tours, Tours, France; si-tahar@univ-tours.fr.|Institut National de la Santé et de la Recherche Médicale, Centre d'Etude des Pathologies Respiratoires, Unite Mixte de Recherche 1100, Tours, France.
authors: Mustapha
authors: M
authors: Si-Tahar
mesh_terms: D056649:Cathepsin G / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000378:metabolism*; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000737:chemistry / Q000378:metabolism*; D018375:Neutrophil Activation; D009504:Neutrophils / Q000378:metabolism*
chemical_list: D055627:Natural Cytotoxicity Triggering Receptor 1; D056649:Cathepsin G
keywords: immunoregulation; natural killer cells; proteolysis; receptors