Submitted July 9, 2008
Accepted October 22, 2008
TLR2-dependent eosinophil interactions with mycobacteria : role of 
-defensins
Virginie Driss, Fanny Legrand, Emmanuel Hermann, Sylvie Loiseau, Yann Guerardel, Laurent Kremer, Estelle Adam, Gaetane Woerly, David Dombrowicz, and Monique Capron*
Inserm U547, Universite Lille 2, Institut Pasteur de Lille, Lille, France
CNRS UMR 8576, Universite des Sciences et Technologies de Lille, Villeneuve d'Ascq, France
Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Universite de Montpellier II et I, CNRS UMR 5235, Montpellier, France
* Corresponding author; email: monique.capron{at}pasteur-lille.fr.
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. Since eosinophils have been recently involved in innate immune responses, we have investigated the direct interactions of eosinophils with Mycobacterium bovis BCG, as a study model. In the present work, we show that live BCG attracts human eosinophils and induces reactive oxygen species (ROS) synthesis, granule protein release and TNF-
secretion. Using anti-TLR2 neutralizing antibodies before eosinophil 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 MAP Kinase and NF-
B pathways. Additionally, 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.
