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Blood, 2 April 2009, Vol. 113, No. 14, pp. 3235-3244. Prepublished online as a Blood First Edition Paper on October 31, 2008; DOI 10.1182/blood-2008-07-166595. This Article Full Text Full Text (PDF) Supplemental Table and Figures All Versions of this Article: blood-2008-07-166595v1 113/14/3235    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Driss, V. Articles by Capron, M. Search for Related Content PubMed PubMed Citation Articles by Driss, V. Articles by Capron, M. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY TLR2-dependent eosinophil interactions with mycobacteria: role of -defensins Virginie Driss1,*, Fanny Legrand1,*, Emmanuel Hermann1, Sylvie Loiseau1, Yann Guerardel2, Laurent Kremer3,4, Estelle Adam1, Gaëtane Woerly1, David Dombrowicz1, and Monique Capron1 1 Inserm U547, Université Lille 2, IFR142, Institut Pasteur de Lille, Lille; 2 Centre National de la Recherche Scientifique (CNRS) UMR 8576, IFR 147, Université des Sciences et Technologies de Lille, Lille; 3 Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques (DIMNP), Université de Montpellier II et I, CNRS, UMR 5235, Montpellier; and 4 Inserm, DIMNP, Montpellier, France 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)– 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)–B pathways. In addition, a mycobacterial wall component, lipomannan, induced a TLR2-dependent eosinophil activation. In addition, we showed that eosinophils express and produce -defensins upon stimulation with BCG and lipomannan and that -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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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