Translocation of Ribosomal Immunostimulant Through an In Vitro-Reconstituted Digestive Barrier Containing M-Like Cells

Abstract

Ribosomal preparations of pathogenic micro-organisms of the upper respiratory tract can be delivered orally for the prevention of recurrent infectious episodes, because they induce mucosal and protective immune responses. The mechanism of mucosal barrier translocation is difficult to study in animal models, little is therefore known about this process. In order to circumvent these problems, we have examined the uptake of ribosomal preparations in three experimental systems that model human intestinal cells. We found that M-like cells displayed a 8.7-fold increase in the uptake of a ribosomal immunostimulant when compared to absorptive or crypt enterocyte-like cells. The product was taken up, translocated, and delivered in the basolateral compartment by cultured M-like cells. No translocation was observed across monolayers of T84 cells (model of crypt cells). Only minimal translocation occured through monolayers of Caco-2 cells (model of absorptive enterocytes). This suggests that, in vivo, colyophilisat is delivered mainly through the M cells overlying lymphoid follicles (Peyer's patches) or nodules of the gut-associated mucosal lymphoid tissue, which are the major inductor sites of mucosal responses. Use of the M-like cell cultured model could be a key step for the development of even more efficient immunostimulators in animals and human.