Development of an improved in vitro model of human intestinal follicle associated epithelia to study cellular and molecular interactions of Candida albicans with M cells

Abstract

International audienceCandida albicans is a commensal inhabitant of the human mucosa causing harmful invasive infections in immuno-compromised patients, taking origin mainly from the gastro-intestinal tract. A better understanding of the mechanisms by which C. albicans interacts with the intestinal mucosa will improve our knowledge of the physiopathology of disseminated candidiasis. C. albicans can grow upon mucosal surfaces in both the yeast and the hyphal forms, the transition from the yeast to the hyphal form playing a key role in its virulence. Mucosal immunity contributes to both commensalism and pathogenicity of the fungus, possibly through presentation of C. albicans antigens to the underlying organized lymphoid structures via transcytosis that could probably be mediated by the specialized epithelial M cells. With this aim, we developed an in vitro model of the human intestinal Follicle Associated Epithelium (FAE) where enterocytes of the Caco-2 cell line in close contact with mucosal lymphocytes differentiate in M cells. Studying adherence, invasion and translocation of C. albicans across co-cultures suggest that C. albicans interacts differentially with M cells / enterocytes co-cultures as compared to mono-layers of Caco-2 cells alone. The uptake mechanism allowing C. albicans to translocate across the co-culture model is under investigation. Moreover, the respective contribution of the yeast and hyphal forms to this process will be studied using KO mutants of C. albicans unable to produce hyphae. Finally the cytokine production resulting from C. albicans and M cells / Caco-2 co-cultures interaction will be studied