Cryptosporidium parvum infection attenuates the ex vivo propagation of murine intestinal enteroids

Xin Tian Zhang, Ai Yu Gong, Yang Wang, Xiqiang Chen, Sheng Yau S Lim, Courtney E. Dolata, Xian-Ming Chen

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 ex vivo model of intestinal cryptosporidiosis employing enteroids from mice. We detected infection of enteroids isolated from immunocompetent adult and neonatal mice after ex vivo 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/β-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 ex vivo propagation of enteroids from mice, providing additional insights into the impact of Cryptosporidium infection on intestinal epithelial growth.

Original languageEnglish (US)
Article numbere13060
JournalPhysiological Reports
Volume4
Issue number24
DOIs
StatePublished - Dec 1 2016

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Cryptosporidium parvum
Cryptosporidium
Infection
Cryptosporidiosis
Low Density Lipoprotein Receptor-Related Protein-5
Wnt Receptors
Catenins
Sporozoites
Stem Cell Factor
Cell Aging
Growth
Developing Countries
Atrophy
Diarrhea
Parasites
Cell Death
Stem Cells
Down-Regulation
Epithelium

All Science Journal Classification (ASJC) codes

  • Physiology (medical)
  • Physiology

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Cryptosporidium parvum infection attenuates the ex vivo propagation of murine intestinal enteroids. / Zhang, Xin Tian; Gong, Ai Yu; Wang, Yang; Chen, Xiqiang; Lim, Sheng Yau S; Dolata, Courtney E.; Chen, Xian-Ming.

In: Physiological Reports, Vol. 4, No. 24, e13060, 01.12.2016.

Research output: Contribution to journalArticle

Zhang, Xin Tian ; Gong, Ai Yu ; Wang, Yang ; Chen, Xiqiang ; Lim, Sheng Yau S ; Dolata, Courtney E. ; Chen, Xian-Ming. / Cryptosporidium parvum infection attenuates the ex vivo propagation of murine intestinal enteroids. In: Physiological Reports. 2016 ; Vol. 4, No. 24.
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