Cryptosporidium parvum Infection of Human Intestinal Xenografts in SCID Mice Induces Production of Human Tumor Necrosis Factor Alpha and Interleukin-8 |
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| Authors: | Karl B. Seydel Tonghai Zhang Gretchen A. Champion Carl Fichtenbaum Paul E. Swanson Saul Tzipori Jeffrey K. Griffiths Samuel L. Stanley Jr. |
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| Affiliation: | Departments of Molecular Microbiology,1. Medicine,2. and Pathology,3. Washington University School of Medicine, St. Louis, Missouri, and Division of Infectious Diseases, Department of Biomedical Sciences, Tufts University School of Veterinary Medicine,4. and Department of Family Health and Community Medicine, Tufts University School of Medicine,5. Boston, Massachusetts |
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| Abstract: | The protozoan parasite Cryptosporidium parvum invades intestinal epithelial cells and can cause life-threatening diarrhea in immunocompromised individuals. Despite the clinical importance of this organism, much remains to be learned about the pathogenesis of C. parvum-induced diarrhea. To explore the role of the intestinal inflammatory response in C. parvum disease, using C. parvum oocysts we infected human intestinal xenografts in severe combined immunodeficient (SCID) mice. Seven days after infection, we found levels of human tumor necrosis factor alpha and interleukin-8 in C. parvum-infected human intestinal xenografts that were significantly higher than those seen in uninfected control xenografts. These results demonstrate that human intestinal cells produce proinflammatory cytokines in response to C. parvum infection and establish SCID-HU-INT mice as a model system to study the interactions of C. parvum with the human intestine. |
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