title: Intestinal Cell Tight Junctions Limit Invasion of Candida albicans through Active Penetration and Endocytosis in the Early Stages of the Interaction of the Fungus with the Intestinal Barrier.
abstract: C. albicans is a commensal yeast of the mucous membranes in healthy humans that can also cause disseminated candidiasis, mainly originating from the digestive tract, in vulnerable patients. It is necessary to understand the cellular and molecular mechanisms of the interaction of C. albicans with enterocytes to better understand the basis of commensalism and pathogenicity of the yeast and to improve the management of disseminated candidiasis. In this study, we investigated the kinetics of tight junction (TJ) formation in parallel with the invasion of C. albicans into the Caco-2 intestinal cell line. Using invasiveness assays on Caco-2 cells displaying pharmacologically altered TJ (i.e. differentiated epithelial cells treated with EGTA or patulin), we were able to demonstrate that TJ protect enterocytes against invasion of C. albicans. Moreover, treatment with a pharmacological inhibitor of endocytosis decreased invasion of the fungus into Caco-2 cells displaying altered TJ, suggesting that facilitating access of the yeast to the basolateral side of intestinal cells promotes endocytosis of C. albicans in its hyphal form. These data were supported by SEM observations of differentiated Caco-2 cells displaying altered TJ, which highlighted membrane protrusions engulfing C. albicans hyphae. We furthermore demonstrated that Als3, a hypha-specific C. albicans invasin, facilitates internalization of the fungus by active penetration and induced endocytosis by differentiated Caco-2 cells displaying altered TJ. However, our observations failed to demonstrate binding of Als3 to E-cadherin as the trigger mechanism of endocytosis of C. albicans into differentiated Caco-2 cells displaying altered TJ.
authors.affiliation: UMR 1347, Univ Bourgogne-Franche Comté, 17 Rue Sully, BP 86 510, F-21065 Dijon Cedex, France.|Centre Hospitalier Universitaire, Service de Parasitologie Mycologie, 2 Rue Angélique Ducoudray, F-21079 Dijon Cedex, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Goyer
authors.affiliation: UMR 1347, Univ Bourgogne-Franche Comté, 17 Rue Sully, BP 86 510, F-21065 Dijon Cedex, France.|Centre Hospitalier Universitaire, Service de Parasitologie Mycologie, 2 Rue Angélique Ducoudray, F-21079 Dijon Cedex, France.
authors.forename: Alicia
authors.initials: A
authors.lastname: Loiselet
authors.affiliation: UMR 1347, Univ Bourgogne-Franche Comté, 17 Rue Sully, BP 86 510, F-21065 Dijon Cedex, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Bon
authors.affiliation: Laboratoire de Parasitologie-Mycologie, Aix-Marseille Univ. Marseille; AP-HM, CHU Timone, F-13385 Marseille cedex 05, France.
authors.forename: Coralie
authors.initials: C
authors.lastname: L'Ollivier
authors.affiliation: Robert Koch-Institute, Centre for Biological Threats and Special Pathogens, Advanced Light and Electron Microscopy, Nordufer 20, 13353 Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Laue
authors.affiliation: Robert Koch-Institute, Centre for Biological Threats and Special Pathogens, Advanced Light and Electron Microscopy, Nordufer 20, 13353 Berlin, Germany.
authors.forename: Gudrun
authors.initials: G
authors.lastname: Holland
authors.affiliation: UMR 1347, Univ Bourgogne-Franche Comté, 17 Rue Sully, BP 86 510, F-21065 Dijon Cedex, France.|Centre Hospitalier Universitaire, Service de Parasitologie Mycologie, 2 Rue Angélique Ducoudray, F-21079 Dijon Cedex, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Bonnin
authors.affiliation: UMR 1347, Univ Bourgogne-Franche Comté, 17 Rue Sully, BP 86 510, F-21065 Dijon Cedex, France.|Centre Hospitalier Universitaire, Service de Parasitologie Mycologie, 2 Rue Angélique Ducoudray, F-21079 Dijon Cedex, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Dalle
mesh_terms: D018938:Caco-2 Cells; D002176:Candida albicans / Q000502:physiology*; D002177:Candidiasis / Q000378:metabolism* / Q000382:microbiology; D004705:Endocytosis; D054884:Host-Pathogen Interactions; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology* / Q000648:ultrastructure; D019108:Tight Junctions / Q000378:metabolism* / Q000382:microbiology* / Q000648:ultrastructure