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Infection and Immunity, June 2003, p. 3034-3042, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3034-3042.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Killing of Aspergillus fumigatus by Alveolar Macrophages Is Mediated by Reactive Oxidant Intermediates

B. Philippe,1,{dagger} O. Ibrahim-Granet,1 M. C. Prévost,2 M. A. Gougerot-Pocidalo,3 M. Sanchez Perez,4 A. Van der Meeren,5 and J. P. Latgé1*

Unité des Aspergillus, Departement Structure et Dynamique des Génomes,1 Plate-Forme de Microscopie Electronique, Institut Pasteur,2 Institut National de la Santé et de la Recherche Médicale U-479, Centre Hospitalier Universitaire Xavier Bichat, Paris,3 Section Autonome de Radiobiologie Appliquée à la Médecine, Département de Protection de la Santé de l'Homme et de Dosimétrie, Institut de la Protection et de la Sûreté Nucléaire, Fontenay-aux-Roses, France,5 Immunologia, Departamento de Microbiologia y Genetica, Universidad de Salamanca, Salamanca, Spain4

Received 10 September 2002/ Returned for modification 23 October 2002/ Accepted 10 February 2003

Phagocytosis and mechanisms of killing of Aspergillus fumigatus conidia by murine alveolar macrophages (AM), which are the main phagocytic cells of the innate immunity of the lung, were investigated. Engulfment of conidia by murine AM lasts 2 h. Killing of A. fumigatus conidia by AM begins after 6 h of phagocytosis. Swelling of the conidia inside the AM is a prerequisite for killing of conidia. The contributions of NADPH oxidase and inducible nitric oxide synthase to the conidicidal activity of AM were studied using AM from OF1, wild-type and congenic p47phox-/- 129Sv, and wild-type and congenic iNOS-/- C57BL/6 mice. AM from p47phox-/- mice were unable to kill A. fumigatus conidia. Inhibitors of NADPH oxidase that decreased the production of reactive oxidant intermediates inhibited the killing of A. fumigatus without altering the phagocytosis rate. In contrast to NADPH oxidase, nitric oxide synthase does not play a role in killing of conidia. Corticosteroids did not alter the internalization of conidia by AM but did inhibit the production of reactive oxidant intermediates and the killing of A. fumigatus conidia by AM. Impairment of production of reactive oxidant intermediates by corticosteroids is responsible for the development of invasive aspergillosis in immunosuppressed mice.

* Corresponding author. Mailing address: Unité des Aspergillus, Institut Pasteur, 25 rue du docteur Roux, F-75724, Paris, France. Phone: 33 1 40 61 35 18. Fax: 33 1 40 61 34 19. E-mail: jplatge{at}pasteur.fr.

Editor: T. R. Kozel

{dagger} Present address: Service de Pneumologie, Hôpital Foch, 92151 Suresnes cedex, France.

Infection and Immunity, June 2003, p. 3034-3042, Vol. 71, No. 6
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.6.3034-3042.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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