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The Journal of Immunology, 2008, 181, 7100-7105
Copyright © 2008 by The American Association of Immunologists, Inc.

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Aspergillus Conidia Activate the Complement by the Mannan-Binding Lectin C2 Bypass Mechanism1

Chantal Dumestre-Pérard2,*,{dagger},{ddagger}, Bertrand Lamy{ddagger}, Delphine Aldebert*,{dagger}, Catherine Lemaire-Vieille*,{dagger}, Renée Grillot§, Jean-Paul Brion, Jean Gagnon*,{dagger} and Jean-Yves Cesbron*,{dagger},{ddagger}

* Laboratoire Adaptation et Pathogénie des Micro-organismes, Université Joseph Fourier, Grenoble 1, BP 170, Grenoble, France; {dagger} Centre National de la Recherche Scientifique Unité Mixte de Recherche 5163; {ddagger} Laboratoire d’Immunologie, Pôle Biologie, § Laboratoire de Parasitologie-Mycologie, Pôle Biologie; and Service des Maladies Infectieuses, Département de Médecine Aigüe et Spécialisée, CHU Grenoble, BP 217, Grenoble, France

Innate immunity is the major host defense against invasive aspergillosis. To determine whether the collectin mannan-binding lectin (MBL) is involved in the initial protective immunity through complement activation against opportunistic fungal infections caused by Aspergillus, we performed in vitro studies on 29 different strains of Aspergillus conidia from five different species. Incubation of Aspergillus conidia in human normal serum leads to activation of the alternative pathway, whereas neither the classical nor the lectin pathways through C4 and C2 cleavage are activated. Complement response to conidia was investigated using a MBL-deficient serum and reconstitution experiments were conducted with MBL/MASPs complexes. We found that MBL can directly support C3 activation by a C2 bypass mechanism. Finally, a stronger activation of the alternative pathway was observed for the clinical strains isolated from patients with invasive aspergillosis, compared with the environmental strains.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

1 This work was supported by funds from the "Programme Hospitalier de Recherche Clinique" Number 2331, CHU Grenoble, France.

2 Address correspondence and reprint requests to Dr. Chantal Dumestre-Pérard, Laboratoire Adaptation et Pathogénie des Micro-organismes, UMR5163 CNRS-UJF, Institut Jean Roget, BP170, 38042 Grenoble, France, E-mail address: Chantal.Dumestre{at}ujf-grenoble.fr

3 Abbreviations used in this paper: MBL, mannan-binding lectin; MASP, MBL associated serine protease; SP, surfactant protein; NHS, normal human serum.




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T. R. T. Dagenais and N. P. Keller
Pathogenesis of Aspergillus fumigatus in Invasive Aspergillosis
Clin. Microbiol. Rev., July 1, 2009; 22(3): 447 - 465.
[Abstract] [Full Text] [PDF]




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