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R&D Laboratory of the Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon, Switzerland
In addition to fulfilling its function of immune exclusion at mucosal surfaces, secretory IgA (SIgA) Ab exhibits the striking feature to adhere selectively to M cells in the mouse and human intestinal Peyer’s patches (PPs). Subsequent uptake drives the SIgA Ab to dendritic cells (DCs), which become partially activated. Using freshly isolated mouse DCs, we found that the interaction with SIgA was tissue and DC subtype dependent. Only DCs isolated from PPs and mesenteric lymph nodes interacted with the Ab. CD11c+CD11b+ DCs internalized SIgA, while CD11c+CD19+ DCs only bound SIgA on their surface, and no interaction occurred with CD11c+CD8
+ DCs. We next examined whether SIgA could deliver a sizeable cargo to PP DCs in vivo by administering SIgA-Shigella flexneri immune complexes into a mouse ligated intestinal loop containing a PP. We found that such immune complexes entered the PPs and were internalized by subepithelial dome PP DCs, in contrast to S. flexneri alone that did not penetrate the intestinal epithelium in mice. Dissemination of intraepithelial S. flexneri delivered as immune complexes was limited to PPs and mesenteric lymph nodes. We propose that preexisting SIgA Abs associated with microbes contribute to mucosal defense by eliciting responses that prevent overreaction while maintaining productive immunity.
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 Grants 3200-068038 and 3200-109545 from the Swiss Science Research Foundation (to B.C.).
2 Address correspondence and reprint requests to Dr. Blaise Corthésy, R&D Laboratory, Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Hôpital Orthopédique 05-1542, Rue du Bugnon, Avenue Pierre Decker 4, CH-1011 Lausanne, Switzerland. E-mail address: blaise.corthesy{at}chuv.ch
3 Abbreviations used in this paper: SIgA, secretory IgA; IFR, interfollicular region; LSC, laser scanning confocal; MLN, mesenteric lymph node; PP, Peyer’s patch; pIgA, polymeric IgA; SC, secretory component; SED, subepithelial dome; DC, dendritic cell; hSC, human SC; LB, Luria-Bertani; BLN, bronchial LN; ILN, inguinal LN.
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