Antigen sampling by epithelial tissues: implication for vaccine design.

Abstract

Mucosal surfaces of the respiratory, digestive and urogenital tracts are covered by a specialized epithelium which constitutes an efficient physical barrier against environmental pathogens. These surfaces differ greatly in their cellular organisation and in antigen sampling. In stratified epithelia, professional antigen-presenting cells, the dendritic cells or Langerhans cells, are intimately associated with the epithelial barrier and take up samples of foreign material from the external environment which they transport to local or distant organized lymphoid tissues. In simple epithelia highly specialised cells, the so-called M cells, sample foreign material and microorganisms and deliver them by transepithelial transport from the lumen to the underlying organized lymphoid tissue (MALT). The interaction of lymphocytes with the follicle-associated epithelium (FAE) is responsible for the loss of digestive functions and the acquisition of transepithelial transport activity. The three way interaction of epithelium, lymphoid cells, and microorganisms seen in the FAE which controls the formation of MALT provides a dramatic demonstration of the phenotypic plasticity of the intestinal epithelium and probably of all simple epithelia. We have shown that all mucosal surfaces, covered by stratified or simple epithelia are able to sample and transport live recombinant bacterial vaccines, which elicit systemic and local immune responses against the carrier and the foreign antigen. In gut and nasal-associated lymphoid tissue, Salmonella are taken up by dendritic cells which form a dense cellular network in the dome regions of MALT. Targeting bacterial vaccine candidates to dendritic or M cells is likely to facilitate their sampling by epithelial tissues and to contribute to strong mucosal and systemic immune responses.