title: Induction of virulence factors in Giardia duodenalis independent of host attachment.
abstract: Giardia duodenalis is responsible for the majority of parasitic gastroenteritis in humans worldwide. Host-parasite interaction models in vitro provide insights into disease and virulence and help us to understand pathogenesis. Using HT-29 intestinal epithelial cells (IEC) as a model we have demonstrated that initial sensitisation by host secretions reduces proclivity for trophozoite attachment, while inducing virulence factors. Host soluble factors triggered up-regulation of membrane and secreted proteins, including Tenascins, Cathepsin-B precursor, cystatin, and numerous Variant-specific Surface Proteins (VSPs). By comparison, host-cell attached trophozoites up-regulated intracellular pathways for ubiquitination, reactive oxygen species (ROS) detoxification and production of pyridoxal phosphate (PLP). We reason that these results demonstrate early pathogenesis in Giardia involves two independent host-parasite interactions. Motile trophozoites respond to soluble secreted signals, which deter attachment and induce expression of virulence factors. Trophozoites attached to host cells, in contrast, respond by up-regulating intracellular pathways involved in clearance of ROS, thus anticipating the host defence response.
authors: Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, NSW 2109, Australia.
authors: Samantha J
authors: SJ
authors: Emery
authors: Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, NSW 2109, Australia.
authors: Mehdi
authors: M
authors: Mirzaei
authors: Microbial Screening Technologies, Pty, Ltd, Smithfield, NSW 2165, Australia.
authors: Daniel
authors: D
authors: Vuong
authors: Australian Proteome Analysis Facility (APAF), Macquarie University, North Ryde, NSW, 2109, Australia.
authors: Dana
authors: D
authors: Pascovici
authors: Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, USA.
authors: Joel M
authors: JM
authors: Chick
authors: Microbial Screening Technologies, Pty, Ltd, Smithfield, NSW 2165, Australia.
authors: Ernest
authors: E
authors: Lacey
authors: Department of Chemistry and Biomolecular Sciences, Macquarie University, North Ryde, NSW 2109, Australia.
authors: Paul A
authors: PA
authors: Haynes
mesh_terms: D002448:Cell Adhesion; D016829:Giardia lamblia / Q000378:metabolism* / Q000472:pathogenicity*; D005873:Giardiasis / Q000469:parasitology*; D019073:HT29 Cells; D006790:Host-Parasite Interactions; D006801:Humans; D008954:Models, Biological; D010641:Phenotype; D040901:Proteomics; D015800:Protozoan Proteins / Q000378:metabolism; D012995:Solubility; D013194:Staining and Labeling; D053058:Trophozoites / Q000378:metabolism; D037521:Virulence Factors / Q000378:metabolism*
chemical_list: D015800:Protozoan Proteins; D037521:Virulence Factors