Secretory IgA Mediates Bacterial Translocation to Dendritic Cells in Mouse Peyer's Patches with Restriction to Mucosal Compartment

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 be...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2007-12, Vol.179 (11), p.7751-7757
Main Authors: Kadaoui, Khalil A, Corthesy, Blaise
Format: Article
Language:English
Subjects:
Animals
Antibodies - metabolism
Bacteria
Bacterial Translocation - immunology
Dendritic Cells - immunology
Dendritic Cells - microbiology
Female
Immunoglobulin A, Secretory - physiology
Intestinal Mucosa - immunology
Intestinal Mucosa - microbiology
Mice
Mice, Inbred BALB C
Peyer's Patches - immunology
Peyer's Patches - microbiology
Peyer's Patches - ultrastructure
Shigella flexneri - immunology
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Summary: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(+)CD8alpha(+) 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.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.179.11.7751