Possible role of secretory IgA controlling commensal homeostasis in the intestine.

Nicolas ROL (to December 2011) and Blaise CORTHESY

In the gastro-intestinal tract, Peyer’s patches have been described as a major inductive site for mucosal secretory IgA (SIgA) responses directed against pathogens. The classical view is that SIgA serves as the first line of defense against microorganisms by agglutining potential invaders and faciliting their clearance by peristaltic and mucociliary movements, a mechanism called immune exclusion.

The laboratory has previously shown that SIgA is not only able to be „retrotransported“ into Peyer’s patches via the associated M cells, but also to deliver a sizeable cargo (S. flexeneri) in the form of SIgA-based immune complexes, resulting in the onset of non-inflammatory type of responses.

Such a novel function raises the question of the possible role of mucosal SIgA in the interplay with commensal bacteria and the contribution of the antibody in bacterial homeostasis. To address this question, commensal bacterial strains, in association or not with SIgA, were administered into a mouse ligated loop comprising a Peyer’s patch. Then, fluorescently labelled bacteria were tracked by laser scanning confocal microscopy at different time points.

We observed that SIgA coating promotes bacterial entry into Peyer’s patches and subsequent internalization by dendritic cells (DCs) in the subepithelial dome (SED) region.

This result is consistent with the fact that SIgA can deliver a sizeable cargo across Peyer’s patches and show that SIgA is involved in the mechanism by which the mucosal immune system permanently checks the content of the intestine. Further, commensal bacteria were tracked in the draining mesenteric lymph nodes (MLN) in which we show that they exist in the form of SIgA-based immune complexes.

After having demonstrated that these SIgA-based immune complexes are engulfed by the DCs present in the SED region, we evaluated the possible role of SIgA in the nature of the immune response of this cell type. Based on different markers of maturation evaluated by flow cytometry, it appeared that the presence of SIgA led to the same low activation of DCs as with bacteria alone.

In summary we demonstrate for the first time, that SIgA appears to play a more important role at the level of bacterial entry into Peyer’s patches than it is implicated in the activation of DCs.

This work contributes to the understanding of the role of SIgA in the immune response and the homeostasis towards the plethora of antigens in contact with the intestinal mucosa.

Lactobacillus rhamnosus (in green) found in a Peyer’s patch dendritic cell (in red) after the administration of the bacteria in a mouse ligated ileal loop. Image acquired by laser scanning confocal microscopy.

Dernière modification le 30.01.2012 - Impressum - Informations juridiques