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* Unité Interactions Hôte-Pathogène, Département de Biologie des Agents Transmissibles, Centre de Recherches du Service de Santé des Armées, La Tronche, France;
Centre National de la Recherche Scientifique, Université Lyon 1, Unité Mixte de Recherche 5086, Institut de Biologie et Chimie des Protéines, Institut Fédératif de Recherche 128, Biosciences Gerland, Lyon, France; and
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel
Inhalational anthrax is a life-threatening infectious disease of considerable concern, especially because anthrax is an emerging bioterrorism agent. The exact mechanisms leading to a severe clinical form through the inhalational route are still unclear, particularly how immobile spores are captured in the alveoli and transported to the lymph nodes in the early steps of infection. We investigated the roles of alveolar macrophages and lung dendritic cells (LDC) in spore migration. We demonstrate that alveolar macrophages are the first cells to phagocytose alveolar spores, and do so within 10 min. However, interstitial LDCs capture spores present in the alveoli within 30 min without crossing the epithelial barrier suggesting a specific mechanism for rapid alveolus sampling by transepithelial extension. We show that interstitial LDCs constitute the cell population that transports spores into the thoracic lymph nodes from within 30 min to 72 h after intranasal infection. Our results demonstrate that LDCs are central to spore transport immediately after infection. The rapid kinetics of pathogen transport may contribute to the clinical features of inhalational anthrax.
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 Grant CO 010808 from the Délégation Générale pour l’Armement and by 135OP3B loi de finances rectificative Etat-Major des Armées from the Service de Santé des Armées. S.J. is the incumbent of the Pauline Recanati Career Development Chair and a Scholar of the Benoziyo Center for Molecular Medicine.
2 Address correspondence and reprint requests to Dr. J.-N. Tournier, Unité Interactions Hôte-Pathogène, Département de Biologie des Agents Transmissibles, Centre de Recherches du Service de Santé des Armées, 24 Avenue des Maquis du Grésivaudan, 38702 La Tronche, France. E-mail address: jntournier{at}crssa.net
3 Abbreviations used in this paper: AM, alveolar macrophage; BAL, bronchoalveolar lavage; DC, dendritic cell; LDC, lung DC; MFI, mean fluorescence intensity; TLN, thoracic lymph node.
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