title: TLR2-dependent eosinophil interactions with mycobacteria: role of alpha-defensins.
abstract: Peripheral blood and tissue eosinophilia are a prominent feature in allergic diseases and during helminth infections. Eosinophil recruitment also frequently occurs upon mycobacterial infections, particularly in lung granuloma. However, the mechanism by which eosinophils interact with mycobacteria remains largely unknown. Because eosinophils recently have been shown to be involved in innate immune responses, we investigated the direct interactions of eosinophils with Mycobacterium bovis BCG as a study model. We show that live BCG attracts human eosinophils and induces reactive oxygen species (ROS) synthesis, granule protein release, and tumor necrosis factor (TNF)-alpha secretion. Using anti-TLR2 neutralizing antibodies before exposure of eosinophils to BCG, we showed a critical role of TLR2 signaling in ROS and eosinophil peroxidase release. BCG-induced eosinophil activation is mediated through the p38 mitogen-activated protein (MAP) kinase and nuclear factor (NF)-kappaB pathways. In addition, a mycobacterial wall component, lipomannan, induced a TLR2-dependent eosinophil activation. In addition, we showed that eosinophils express and produce alpha-defensins upon stimulation with BCG and lipomannan and that alpha-defensins could inhibit mycobacterial growth in synergy with eosinophil cationic protein. These results suggest a role for human eosinophils as direct effectors in TLR2-mediated innate immunity against mycobacteria and confer to these cells potent cytotoxic functions through defensin and eosinophil cationic protein production.
authors.affiliation: Inserm U547, Université Lille 2, IFR142, Institut Pasteur de Lille, Lille, France.
authors.forename: Virginie
authors.initials: V
authors.lastname: Driss
authors.forename: Fanny
authors.initials: F
authors.lastname: Legrand
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Hermann
authors.forename: Sylvie
authors.initials: S
authors.lastname: Loiseau
authors.forename: Yann
authors.initials: Y
authors.lastname: Guerardel
authors.forename: Laurent
authors.initials: L
authors.lastname: Kremer
authors.forename: Estelle
authors.initials: E
authors.lastname: Adam
authors.forename: Gaëtane
authors.initials: G
authors.lastname: Woerly
authors.forename: David
authors.initials: D
authors.lastname: Dombrowicz
authors.forename: Monique
authors.initials: M
authors.lastname: Capron
mesh_terms: D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000502:physiology; D004804:Eosinophils / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology / Q000502:physiology; D009163:Mycobacterium bovis / Q000254:growth & development / Q000276:immunology* / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D023084:alpha-Defensins / Q000378:metabolism / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism / Q000502:physiology
chemical_list: C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D023084:alpha-Defensins; D048051:p38 Mitogen-Activated Protein Kinases