title: Newly visualized fibrillar collagen scaffolds dictate Entamoeba histolytica invasion route in the human colon.
abstract: The extracellular matrix (ECM) and its role in the outcome of infectious diseases have been poorly investigated. In this study, we determined the impact of the collagen fibres architecture on the invasive process of the enteric parasite Entamoeba histolytica. The behaviour of E. histolytica wild-type and silenced for the cysteine protease A5 (CP-A5) were compared on a three-dimensional collagen matrix and within human colon fragments for fibrillar collagen cleavage and migration. The interstitial collagen fibres within the connective tissue of the human colon, visualized by multiphoton and second harmonic generation signals imaging, presented a dense scaffold at the subepithelial level and a loose meshwork within the chorion. To penetrate the tissue, E. histolytica migrated on the dense scaffold that remained intact, reached the crypt of Lieberkhün, migrated along and then disorganized the loose scaffold to escape into the mucosa. Interestingly, in vitro, CP-A5 was not required for collagenase activity and migration through the matrix but was necessary within the tissue environment for collagen meshwork remodelling and subsequent invasion. The data point out that further step of invasion relay with ECM destruction that requires human components induced or activated in the presence of CP-A5.
authors.affiliation: Institut Pasteur, Unité Biologie Cellulaire du Parasitisme, Paris, France. INSERM U786, Paris, France.
authors.forename: Roman
authors.initials: R
authors.lastname: Thibeaux
authors.forename: Alexandre
authors.initials: A
authors.lastname: Dufour
authors.forename: Pascal
authors.initials: P
authors.lastname: Roux
authors.forename: Michèle
authors.initials: M
authors.lastname: Bernier
authors.forename: Anne-Catherine
authors.initials: AC
authors.lastname: Baglin
authors.forename: Pascal
authors.initials: P
authors.lastname: Frileux
authors.forename: Jean Chrisophe
authors.initials: JC
authors.lastname: Olivo-Marin
authors.forename: Nancy
authors.initials: N
authors.lastname: Guillén
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Labruyère
mesh_terms: D002465:Cell Movement; D003106:Colon / Q000469:parasitology* / Q000473:pathology*; D003238:Connective Tissue / Q000469:parasitology / Q000473:pathology; D004748:Entamoeba histolytica / Q000472:pathogenicity*; D024022:Fibrillar Collagens / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000469:parasitology / Q000473:pathology; D036641:Microscopy, Fluorescence, Multiphoton
chemical_list: D024022:Fibrillar Collagens