Cryptosporidium infection of human intestinal epithelial cells increases expression of osteoprotegerin: A novel mechanism for evasion of host defenses

Alejandro Castellanos-Gonzalez, Linda S. Yancey, Heuy Ching Wang, Birte Pantenburg, Kathleen R. Liscum, Dorothy E. Lewis, A. Clinton White

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Cryptosporidium parasites are pathogens of human intestinal epithelial cells. To determine which genes are regulated during early infection, human ileal mucosa cultured as explants was infected with C. parvum or C. hominis, and gene expression was analyzed by microarray. The gene for osteoprotegerin (OPG) was up-regulated by both parasites. OPG mRNA was also significantly increased in biopsy specimens obtained from a volunteer experimentally infected with C. meleagridis, compared with levels in a prechallenge biopsy specimen. After in vitro infection of HCT-8 cells, there was an early peak in production of OPG mRNA protein. Treatment of infected cells with the OPG ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induced epithelial cell apoptosis and reduced parasite numbers, and recombinant OPG blocked these effects. These results suggest a novel TRAIL-mediated pathway for elimination of Cryptosporidium infection and a role for OPG in modulating this host response.

Original languageEnglish (US)
Pages (from-to)916-923
Number of pages8
JournalJournal of Infectious Diseases
Volume197
Issue number6
DOIs
StatePublished - Mar 15 2008

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

Fingerprint Dive into the research topics of 'Cryptosporidium infection of human intestinal epithelial cells increases expression of osteoprotegerin: A novel mechanism for evasion of host defenses'. Together they form a unique fingerprint.

  • Cite this