期刊
PHYSIOLOGICAL REPORTS
卷 4, 期 24, 页码 -出版社
WILEY
DOI: 10.14814/phy2.13060
关键词
C. parvum; cryptosporidiosis; cytokines; enteroids; intestine; Lgr5; mice; neonatal; stem cells
类别
资金
- National Institutes of Health [AI116323]
- Nebraska Stem Cell Research Program [LB606]
- Nebraska Department of Health & Human Services (DHHS) [LB595]
- National Center for Research Resources [G20RR024001]
Cryptosporidium, a ubiquitous coccidian protozoan parasite that infects the gastrointestinal epithelium and other mucosal surfaces, is an important opportunistic pathogen for immunocompromised individuals and a common cause of diarrhea in young children in the developing countries. One of the pathological hallmarks of intestinal cryptosporidiosis is villous atrophy, which results in a shorter height of intestinal villi. Here, we investigated the effects of Cryptosporidium infection on intestinal epithelial growth, using an exvivo model of intestinal cryptosporidiosis employing enteroids from mice. We detected infection of enteroids isolated from immunocompetent adult and neonatal mice after exvivo exposure to Cryptosporidium sporozoites. We observed a significant inhibition of enteroid propagation following infection. Intriguingly, we identified a decreased expression level of intestinal stem cell markers in enteroids following C.parvum infection. We further measured the expression levels of several Wnt antagonists or agonists in infected enteroids, as induction of the Wnt/-catenin activation is a key factor for intestinal stem cell function. We detected a markedly increased level of the Dickkopf-related protein 1 and decreased level of the Wnt family member 5a in enteroids after infection. The low density lipoprotein receptor-related protein 5, one of the Wnt co-receptors, is downregulated in the infected enteroids. In addition, increased apoptotic cell death and cell senescence were observed in the infected enteroids. Our results demonstrate a significant inhibitory effect of Cryptosporidium infection on the exvivo propagation of enteroids from mice, providing additional insights into the impact of Cryptosporidium infection on intestinal epithelial growth.
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