Entry sites for oral vaccines and drugs: A role for M cells, enterocytes and dendritic cells?

M cells have long been considered as the unique entry site of macromolecule s and pathogens in the intestine, allowing delivery to antigen-presenting c ells in the Peyer's patches. Therefore, antigen formulation for the develop ment of oral vaccines has been based on administration of antigens in the f orm of live replicating pathogens or soluble antigen vectorized into biodeg radable microspheres. However, progress in the understanding of the biology of dendritic cells, as well as identification of their localization at dif ferent sites of the intestine, suggest that they may capture antigen direct ly from the lumen of mucosal tissues or from epithelial cells of the intest ine. Besides, a role for the absorptive epithelium, in antigen presentation through both classical or non-classical MHC elements suggests that PP may not be the exclusive inductive site of the immune response in the gut. Thus , depending on the nature of the antigen (soluble or infectious) there may be different sites of antigen entry through the intestine, and each site ma y have distinct efficiency to promote a protective immune response, dependi ng on the presence and function of dendritic cells. Cross talk between M ce lls, epithelial cells and dendritic cells may play an important role in det ermining the outcome of tolerance versus immunity.