Targeting of Secretory IgA to Peyer’s Patch Dendritic and T Cells after Transport by Intestinal M Cells

Abstract

In addition to being instrumental to the protection of mucosal epithelia, secretory IgA (SIgA) adheres to and is transported by intestinal Peyer’s patch (PP) M cells. The possible functional reason for this transport is unknown. We have thus examined in mice the outcome of SIgA delivered from the intestinal lumen to the cells present in the underlying organized mucosa-associated lymphoreticular tissue. We show selective association of SIgA with dendritic cells and CD4+ T and B lymphocytes recovered from PP in vitro. In vivo, exogenously delivered SIgA is able to enter into multiple PP lining the intestine. In PP, SIgA associates with and is internalized by dendritic cells in the subepithelial dome region, whereas the interaction with CD4+ T cells is limited to surface binding. Interaction between cells and SIgA is mediated by the IgA moiety and occurs for polymeric and monomeric molecular forms. Thus, although immune exclusion represents the main function of SIgA, transport of the Ab by M cells might promote Ag sampling under neutralizing conditions essential to the homeostasis of mucosal surfaces.

Roundtrip Ticket for Secretory IgA: Role in Mucosal Homeostasis?

“…In vivo uptake of SIgA delivered into mouse ligated ileal loop containing a Peyer's patch resulted in specific targeting to DC in the SED region and CD4 ϩ T cells in the IFR (57). As for binding to M cells, the interaction of SIgA with DC was dependent on the IgA moiety.…”

“…As for binding to M cells, the interaction of SIgA with DC was dependent on the IgA moiety. SIgA was internalized into DC, whereas the association with CD4 ϩ T cells was limited to cell surface (57). Ex vivo, only DC isolated from Peyer's patches and MLN showed selective binding and internalization mimicking the in vivo situation (K. Kadaoui and B. Corthésy, unpublished data); DC from the spleen and other lymph nodes did not exhibit any association, arguing for a specific receptor still to be identified.…”

Delivery strategies to enhance oral vaccination against enteric infections

“…SIgA is the main Ig isotype associated with gut immune responses and has also been implicated in the transport of antigens from the lumen of the gut across the epithelium [61,62]. SIgA containing complexes have been shown to be transcytosed through M cells to APCs and lymphocytes in the subepithelial dome (SED) [61,62]. Although no specific apical receptor for SIgA complexes has been described, Dectin-1 has been implicated as an important player in this process [63].…”

“…Moreover, intestinal SIgA antibodies against the B subunit of CT (CTB) are known correlates of oral vaccine efficacy in humans and SIgA against bacterial colonisation factors has been established as one of the key mediators of intestinal immunity to ETEC infections [99]. Thus SigA can act in the exclusion and excretion of antigens in addition to potentially enhancing local immune responses by targeting antigens specifically to M cells [62].…”

“…LPS antigens have been shown to be protective in the case of the oral cholera vaccine [5], and so targeting such receptors may offer a novel approach to enhance the uptake of LPSbased antigens. SIgA is the main Ig isotype associated with gut immune responses and has also been implicated in the transport of antigens from the lumen of the gut across the epithelium [61,62]. SIgA containing complexes have been shown to be transcytosed through M cells to APCs and lymphocytes in the subepithelial dome (SED) [61,62].…”