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 macromolecules and pathogens in the intestine, allowing delivery to antigen-presenting cells in the Peyer's patches. Therefore, antigen formulation for the development of oral vaccines has been based on administration of antigens in the form of live replicating pathogens or soluble antigen vectorized into biodegradable microspheres. However, progress in the understanding of the biology of dendritic cells, as well as identification of their localization at different sites of the intestine, suggest that they may capture antigen directly from the lumen of mucosal tissues or from epithelial cells of the intestine. 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 may have distinct efficiency to promote a protective immune response, depending on the presence and function of dendritic cells. Cross talk between M cells, epithelial cells and dendritic cells may play an important role in determining the outcome of tolerance versus immunity. Copyright 1999 Academic Press.