title: Host cell tropism underlies species restriction of human and bovine Cryptosporidium parvum genotypes.
abstract: It has been recognized recently that human cryptosporidiosis is usually caused by Cryptosporidium parvum genotype I ("human" C. parvum), which is not found in animals. Compared to C. parvum genotype II, little is known of the biology of invasion of the human-restricted C. parvum genotype I. The aims of the present study were (i) to explore and compare with genotype II the pathogenesis of C. parvum genotype I infection by using an established in vitro model of infection and (ii) to examine the possibility that host-specific cell tropism determines species restriction among C. parvum genotypes by using a novel ex vivo small intestinal primary cell model of infection. Oocysts of C. parvum genotypes I and II were used to infect HCT-8 cells and primary intestinal epithelial cells in vitro. Primary cells were harvested from human endoscopic small-bowel biopsies and from bovine duodenum postmortem. C. parvum genotype I infected HCT-8 cells with lower efficiency than C. parvum genotype II. Actin colocalization at the host parasite interface and reduction in levels of invasion after treatment with microfilament inhibitors (cytochalasin B and cytochalasin D) were observed for both genotypes. C. parvum genotype II invaded primary intestinal epithelial cells, regardless of the species of origin. In contrast, C. parvum genotype I invaded only human small-bowel cells. The pathogenesis of C. parvum genotype I differs from C. parvum genotype II. C parvum genotype I does not enter primary bovine intestinal cells, suggesting that the species restriction of this genotype is due to host tissue tropism of the infecting isolate.
authors.affiliation: The Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin, Ireland.
authors.forename: Amna
authors.initials: A
authors.lastname: Hashim
authors.forename: Marguerite
authors.initials: M
authors.lastname: Clyne
authors.forename: Grace
authors.initials: G
authors.lastname: Mulcahy
authors.forename: Donna
authors.initials: D
authors.lastname: Akiyoshi
authors.forename: Rachel
authors.initials: R
authors.lastname: Chalmers
authors.forename: Billy
authors.initials: B
authors.lastname: Bourke
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D003457:Cryptosporidiosis / Q000469:parasitology* / Q000473:pathology*; D016785:Cryptosporidium parvum / Q000145:classification / Q000187:drug effects / Q000235:genetics* / Q000502:physiology*; D003599:Cytoskeleton / Q000378:metabolism / Q000469:parasitology; D005838:Genotype; D006801:Humans; D007422:Intestines / Q000166:cytology / Q000469:parasitology; D008870:Microtubules / Q000187:drug effects; D033661:Oocysts / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D013045:Species Specificity
chemical_list: D000199:Actins