title: Giardia duodenalis assemblage-specific induction of apoptosis and tight junction disruption in human intestinal epithelial cells: effects of mixed infections.
abstract: In view of the interest in genotype-specific pathogenesis in Giardia duodenalis , the aim of the present study was to examine the effects of infection with different, or mixed, G. duodenalis assemblages on the integrity of human intestinal epithelia. To that end, human epithelial cells (HCT-8) were cultured and exposed to different G. duodenalis assemblages (A, B, and E) or a combination of these assemblages. Epithelial disruption and apoptosis were evaluated by fluorescent microscopy and apoptotic oligonucleosome quantification. The results indicate that infection with trophozoites disrupts epithelial tight junctions and induces varying degrees of enterocyte apoptosis, depending on the infecting assemblage. All disruptions were caspase-3 dependent and were more pronounced when caused by a non-host specific assemblage. Furthermore, infections by isolates in combination with isolates from another assemblage enhanced the epithelial disruption and apoptosis. Further studies in vitro and in vivo are required to confirm the mechanisms of enhanced pathogenicity of mixed or non-host specific (or both) G. duodenalis infections. Findings in the present study point to the potential pathogenic importance of intra-species polyparasitism in giardiasis.
authors.affiliation: School of Veterinary and Biomedical Sciences, Murdoch University, Western Australia.
authors.forename: Wan Hon
authors.initials: WH
authors.lastname: Koh
authors.forename: Thomas
authors.initials: T
authors.lastname: Geurden
authors.forename: Tim
authors.initials: T
authors.lastname: Paget
authors.forename: Ryan
authors.initials: R
authors.lastname: O'Handley
authors.forename: Robert F
authors.initials: RF
authors.lastname: Steuart
authors.forename: R C Andrew
authors.initials: RC
authors.lastname: Thompson
authors.forename: Andre G
authors.initials: AG
authors.lastname: Buret
mesh_terms: D000230:Adenocarcinoma; D017209:Apoptosis; D053148:Caspase 3 / Q000187:drug effects; D061945:Caspase Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000469:parasitology* / Q000473:pathology; D016829:Giardia lamblia / Q000145:classification / Q000472:pathogenicity*; D006801:Humans; D007078:Ileal Neoplasms; D007080:Ileocecal Valve; D007413:Intestinal Mucosa / Q000469:parasitology* / Q000473:pathology; D019108:Tight Junctions / Q000469:parasitology* / Q000473:pathology; D053058:Trophozoites / Q000145:classification / Q000254:growth & development; D014407:Tumor Cells, Cultured
chemical_list: D061945:Caspase Inhibitors; D053148:Caspase 3