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Impact of Bronchial Epithelium on Dendritic Cell Migration and Function: Modulation by the Bacterial Motif KpOmpA¹

Muriel Pichavant^*, Solenne Taront^*, Pascale Jeannin, Laëtitia Breuilh^*, Anne-Sophie Charbonnier, Corentin Spriet, Catherine Fourneau^*, Nathalie Corvaia^¶, Laurent Héliot, Anne Brichet^||, André-Bernard Tonnel^*,||, Yves Delneste and Philippe Gosset^2,*

^* Institut National de la Santé et de la Recherche Médicale (INSERM) U774, Institut Pasteur de Lille, Lille, France; INSERM U564, University Hospital of Angers, Angers, France; INSERM U459, Centre Hospitalier Régional Universitaire (CHRU), Lille, France; Plateau d’Imagerie Cellulaire, Institut de Biologie de Lille, Lille, France; ^¶ Centre d’Immunologie Pierre Fabre, St Julien en Genevois, France; and ^|| Clinique des Maladies Respiratoires, CHRU, Lille, France

Mucosal immune response depends on the surveillance network established by dendritic cells (DC), APC localized within the epithelium. Bronchial epithelial cells (BEC) play a pivotal role both in the host defense and in the pathogenesis of inflammatory airway disorders. We previously showed that the outer membrane protein A from Klebsiella pneumoniae (KpOmpA), a pathogen-associated molecular pattern (PAMP) derived from Klebsiella pneumoniae, activates BEC. In this study, we evaluated the consequences of this activation on DC traffic and functions. KpOmpA significantly increased the production of CCL2, CCL5, CXCL10, and CCL20 by BEC. Stimulation of BEC increased their chemotactic activity for monocyte-derived DC (MDDC) precursors, through CCL5 and CXCL10 secretion. BEC/MDDC precursor coculture leads to an ICAM-1-dependent accelerated differentiation and enhanced maturation of MDDC. BEC/DC interactions did not affect the capacity of DC to induce T cell proliferation. However, DC preincubated with BEC increased significantly the IL-10 production by autologous T cells. Basolateral and intraepithelial DC differently enhance IL-4 and/or IL-10 synthesis according to the condition of stimulation. In vivo, intranasal injections of KpOmpA into BALB/c mice induced the recruitment of CD11c⁺ and I-A^d+ myeloid DC associated with bronchial epithelium activation as evidenced by CCL20 expression. These data show that KpOmpA-exposed BEC participate in the homeostasis of myeloid DC network, and regulate the induction of local immune response.

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 S.T. was a recipient of a fellowship from Agence de l’Environnement et de la Maîtrise de l’Energie. C.S. was supported by Région Nord-Pas-de-Calais PhD fellowship.

² Address correspondence and reprint requests to Dr. Philippe Gosset, Institut National de la Santé et de la Recherche Médicale, Unité 774, Institut Pasteur, 1, rue du Professeur Calmette, BP 245, 59019 Lille cedex, France. E-mail address: Philippe.Gosset{at}pasteur-lille.fr

³ Abbreviations used in this paper: DC, dendritic cell; BAL, bronchoalveolar lavage; BEC, bronchial epithelial cell; KpOmpA, outer membrane protein A from Klebsiella pneumoniae; LC, Langerhans cell; DC, dendritic cell; MDDC, monocyte-derived DC; PAMP, pathogen-associated molecular pattern.