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Infection and Immunity, December 2009, p. 5537-5542, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.01457-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

CD23 Mediates Antimycobacterial Activity of Human Macrophages{triangledown}

M. Djavad Mossalayi,1* Ioannis Vouldoukis,2 Maria Mamani-Matsuda,1 Tina Kauss,1 Jean Guillon,3 Jeanne Maugein,4 Daniel Moynet,1 Jérôme Rambert,1 Vanessa Desplat,1 Dominique Mazier,2 Philippe Vincendeau,1 and Denis Malvy1

Laboratoire d'Immunologie et Parasitologie, UFR des Sciences Pharmaceutiques, Université Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France,1 INSERM U511 Immuno-Biologie Cellulaire et Moléculaire des Infections Parasitaires, Université Pierre et Marie Curie, 91 Boulevard de l'Hôpital, 75013 Paris, France,2 EA 4138-Pharmacochimie, UFR des Sciences Pharmaceutiques, Université Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France,3 Laboratoire de Bactériologie, CHU de Bordeaux, Hôpital du Haut-Lévêque, Avenue de Magellan, 33 604 Pessac, France4

Received 28 November 2008/ Returned for modification 5 February 2009/ Accepted 17 September 2009

Engagement of surface receptors contributes to the antimicrobial activity of human immune cells. We show here that infection of human monocyte-derived macrophages (MDM) with live Mycobacterium avium induced the expression of CD23 on their membrane. Subsequent cross-linking of surface CD23 by appropriate ligands induced a dose-dependent antibacterial activity of MDM and the elimination of most infected cells. The stimulation of inducible nitric oxide synthase-dependent generation of NO from MDM after CD23 activation played a major role during their anti-M. avium activity. CD23 activation also induced tumor necrosis factor alpha (TNF-{alpha}) production from MDM. Mycobacteria reduction was partially inhibited by the addition of neutralizing anti-TNF-{alpha} antibody to cell cultures without affecting NO levels, which suggested the role of this cytokine for optimal antimicrobial activity. Finally, interleukin-10, a Th2 cytokine known to downregulate CD23 pathway, is shown to decrease NO generation and mycobacteria elimination by macrophages. Therefore, (i) infection with M. avium promotes functional surface CD23 expression on human macrophages and (ii) subsequent signaling of this molecule contributes to the antimicrobial activity of these cells through an NO- and TNF-{alpha}-dependent pathway. This study reveals a new human immune response mechanism to counter mycobacterial infection involving CD23 and its related ligands.

* Corresponding author. Mailing address: Laboratoire d'Immunologie et Parasitologie, Faculté de Pharmacie, Université Victor Segalen-Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France. Phone: 33 557 571 243. Fax: 33 557 571 210. E-mail: djavad.mossalayi{at}u-bordeaux2.fr

{triangledown} Published ahead of print on 5 October 2009.

Editor: J. L. Flynn

Infection and Immunity, December 2009, p. 5537-5542, Vol. 77, No. 12
0019-9567/09/$08.00+0     doi:10.1128/IAI.01457-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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