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*Institut National de la Recherche Agronomique, Unité Mixte de Recherche 1225, Toulouse, France;
Université de Toulouse, Ecole Nationale Vétérinaire Toulouse, Unité Mixte de Recherche 1225, Toulouse, France;
Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris, France;
INSERM U 786, Paris, France; and
¶Laboratoire R&D du Service d’Immunologie et d’Allergie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland
Shigella, a Gram-negative invasive enteropathogenic bacterium responsible for bacillary dysentery, causes the rupture, invasion, and inflammatory destruction of the human colonic mucosa. We explored the mechanisms of protection mediated by Shigella LPS-specific secretory IgA (SIgA), the major mucosal Ab induced upon natural infection. Bacteria, SIgA, or SIgA-S. flexneri immune complexes were administered into rabbit ligated intestinal loops containing a Peyer’s patch. After 8 h, localizations of bacteria, SIgA, and SIgA-S. flexneri immune complexes were examined by immunohistochemistry and confocal microscopy imaging. We found that anti-Shigella LPS SIgA, mainly via immune exclusion, prevented Shigella-induced inflammation responsible for the destruction of the intestinal barrier. Besides this luminal trapping, a small proportion of SIgA-S. flexneri immune complexes were shown to enter the rabbit Peyer’s patch and were internalized by dendritic cells of the subepithelial dome region. Local inflammatory status was analyzed by quantitative RT-PCR using newly designed primers for rabbit pro- and anti-inflammatory mediator genes. In Peyer’s patches exposed to immune complexes, limited up-regulation of the expression of proinflammatory genes, including TNF-
, IL-6, Cox-2, and IFN-
, was observed, consistent with preserved morphology. In contrast, in Peyer’s patches exposed to Shigella alone, high expression of the same mediators was measured, indicating that neutralizing SIgA dampens the proinflammatory properties of Shigella. These results show that in the form of immune complexes, SIgA guarantees both immune exclusion and neutralization of translocated bacteria, thus preserving the intestinal barrier integrity by preventing bacterial-induced inflammation. These findings add to the multiple facets of the noninflammatory properties of SIgA.
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 Institut Pasteur and INSERM (to A.P.), by Grants 3200–109545 and 3200–122039 from the Swiss Science Research Foundation (to B.C.), and grants from Région Midi-Pyrénées (no. A2639), Institut National de la Recherche Agronomique and Ministère de l’Agriculture et de la Pêche, Direction Générale de l’Enseignement Supérieur et de la Recherche (to S.B.).
2 Address correspondence and reprint requests to Dr. Armelle Phalipon, Unité de Pathogénie Microbienne Moléculaire, INSERM U786, Institut Pasteur, 28 rue du Dr. Roux, 75015 Paris, France. E-mail address: armelle.phalipon{at}pasteur.fr
3 Abbreviations used in this paper: SIgA, secretory IgA; DC, dendritic cell; EC, epithelial cell; HPRT, hypoxanthine phosphoribosyltransferase; hSC, human SC; LB, Luria-Bertani; pIgA, polymeric IgA; pIgR, polymeric Ig receptor; PP, Peyer’s patch; SC, secretory component; SED, subepithelial dome; TTSS, type III secretion system.
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