TY - JOUR
T1 - Cryptosporidium infection of human intestinal epithelial cells increases expression of osteoprotegerin
T2 - A novel mechanism for evasion of host defenses
AU - Castellanos-Gonzalez, Alejandro
AU - Yancey, Linda S.
AU - Wang, Heuy Ching
AU - Pantenburg, Birte
AU - Liscum, Kathleen R.
AU - Lewis, Dorothy E.
AU - White, A. Clinton
N1 - Funding Information:
Received 12 June 2007; accepted 5 September 2007; electronically published 20 February 2008. Potential conflicts of interest: none reported. Presented in part: Annual Meeting of the American Society of Tropical Medicine and Hygiene, Atlanta, 12–16 November 2006 (poster 263). Financial support: National Institutes of Health (grant R01 AI041735I). Reprints or correspondence: Dr. A. Clinton White, Director, Infectious Disease Div., Dept. of Internal Medicine, University of Texas Medical Branch, 301 University Blvd., Rt. 0435, Galveston, TX 77555-0435 ([email protected]).
PY - 2008/3/15
Y1 - 2008/3/15
N2 - 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.
AB - 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.
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U2 - 10.1086/528374
DO - 10.1086/528374
M3 - Article
C2 - 18288900
AN - SCOPUS:40949124848
SN - 0022-1899
VL - 197
SP - 916
EP - 923
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 6
ER -