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Infection and Immunity, October 2004, p. 6125-6131, Vol. 72, No. 10
0019-9567/04/$08.00+0 DOI: 10.1128/IAI.72.10.6125-6131.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
The Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin,1 Departments of Paediatrics,2 Veterinary Microbiology and Parasitology Conway Institute for Biomolecular and Biomedical Research, University College, Dublin, Ireland,3 Division of Infectious Diseases, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts,4 Cryptosporidium Reference Unit, NPHS Microbiology Swansea, Singleton Hospital, Swansea, Wales, United Kingdom5
Received 31 March 2004/ Returned for modification 22 May 2004/ Accepted 15 July 2004
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.
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