Dectin-1 Is Essential for Reverse Transcytosis of Glycosylated SIgA-Antigen Complexes by Intestinal M Cells

Abstract

This work reports the long-awaited identification of Dectin-1 and Siglec-5 as the M cell co-receptors that mediate the reverse transcytosis of secretory IgA molecules to mount a gut immune response.

Delivery strategies to enhance oral vaccination against enteric infections

“…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]. Therefore exploiting S-IgA specific epithelial receptors may offer opportunities to enhance antigen uptake following oral delivery.…”

Roles of M cells in infection and mucosal vaccines

“…Both the Cɑ1 region and glycosylation, more particularly sialic acid residues, take part in M-cell-mediated reverse transcytosis, and M cells take up SIgA via the Dectin-1 receptor, in which Siglec-5 may act as a co-receptor. 42 There are several mechanisms of targeting M cells for induction of mucosal SIgA responses in animal models. For instance, it has been demonstrated that M cell targeting mediated by a Claudin-4-specific targeting peptide enhances mucosal IgA responses above the response to nontargeted mucosal antigen, which have promise in delivery of mucosal vaccination.…”

Role of secretory IgA in the mucosal sensing of commensal bacteria

“…In addition to its well documented role in pathogen neutralization and clearance, 7,8,10 SIgA is endowed with the capacity to selectively retro-transport bound antigens back into intestinal Peyer's patches across microfold (M) cells 17 via the Dectin-1 receptor expressed at their surface. 18 In the subepithelial dome (SED) region, SIgA-based immune complexes associate with dendritic cells (DCs), 19 resulting in the onset of immunomodulatory types of responses. 20 Seminal papers published by the team of John Cebra more than 2 decades ago have demonstrated that at weaning, up to 70% of commensal bacteria are coated with natural SIgA in the mouse gastrointestinal tract, and that this association is instrumental to the maintenance of bacterial homeostasis; 21,22 the same holds true for pigs and calves.…”