Past project's Collaborator
Nicolas ROL (to December 2011)
In collaboration with Laurent Favre and Jalil Benyacoub,
Nestlé Research Center
The mammalian gastrointestinal (GI)tract harbors a diverse population of commensal species collectively known as the microbiota, which continuously interacts with the host. From very early in life, secretory IgA (SIgA) is found in association with intestinal bacteria. It is considered that this helps to ensure self-limiting growth of the microbiota, and hence participates in symbiosis. In this project, we examine the possible role of SIgA in the transport of commensal bacteria across the GI epithelium. The entry of commensal bacteria in Peyer’s patches (PP) via the M cell pathway is mediated by their association with SIgA. Pre-association of bacteria with non-specific SIgA increases their dynamics of entry and restored the reduced transport observed in germ-free mice known to have a marked reduction in intestinal SIgA production. Selective SIgA-mediated targeting of bacteria is restricted to the tolerogenic CD11c+CD11b+CD8- dendritic cell (DC) subset located in the subepithelial dome region of PPs, confirming that the host is not ignorant of its resident commensals. SIgA-mediated monitoring of commensal bacteria targeting DCs in the subepithelial dome region of PPs represents a mechanism whereby the host’s mucosal immune system controls the continuous dialogue between the host and commensal bacteria.
A, Detection by laser scanning confocal microscopy (LSCM) of FITC-commensal-SIgA complexes 6 hours post-administration in a mouse ligated intestinal loop. Magnifications of the subepithelial dome region demonstrate surface (yellow) and internal (green) co-localization with red-labeled dendritic cells. 3D reconstructed image (bottom left) and orthogonal projections of the same image along the x- and y-axes (bottom right).
B, LSCM image acquired 2 hours after administration of preformed FITC-commensal-SIgA complexes in a mouse ligated intestinal loop. Magnifications of M cell-rich areas demonstrate the presence of LPR-SIgA complexes at the surface and within M cells in 3D reconstructed images (panels 1, 2 and 3). V, villus; L, lumen