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Cryptosporidium parvum disrupts intestinal epithelial barrier in neonatal mice through downregulation of cell junction molecules.

Authors :
Luo, Chaowei
Xu, Yanhua
Zhang, Jie
Tian, Qing
Guo, Yaqiong
Li, Na
Feng, Yaoyu
Xu, Rui
Xiao, Lihua
Source :
PLoS Neglected Tropical Diseases; 5/25/2024, Vol. 18 Issue 5, p1-19, 19p
Publication Year :
2024

Abstract

Background: Cryptosporidium spp. cause watery diarrhea in humans and animals, especially in infants and neonates. They parasitize the apical surface of the epithelial cells in the intestinal lumen. However, the pathogenesis of Cryptosporidium-induced diarrhea is not fully understood yet. Methodology/principal findings: In this study, we infected C57BL/6j neonatal mice with C. parvum IIa and IId subtypes, and examined oocyst burden, pathological changes, and intestinal epithelial permeability during the infection. In addition, transcriptomic analyses were used to study the mechanism of diarrhea induced by the C. parvum IId subtype. The neonatal mice were sensitive to both C. parvum IIa and IId infection, but the IId subtype caused a wide oocyst shedding window and maintained the high oocyst burden in the mice compared with the IIa subtype. In addition, the mice infected with C. parvum IId resulted in severe intestinal damage at the peak of infection, leading to increased permeability of the epithelial barrier. The KEGG, GO and GSEA analyses revealed that the downregulation of adherens junction and cell junction molecules at 11 dpi. Meanwhile, E-cadherin, which is associated with adherens junction, was reduced at the protein level in mouse ileum at peak and late infection. Conclusions/significance: C. parvum IId infection causes more severe pathological damage than C. parvum IIa infection in neonatal mice. Furthermore, the impairment of the epithelial barrier during C. parvum IId infection results from the downregulation of intestinal junction proteins. Author summary: Cryptosporidiosis is a leading cause of moderate to severe diarrhea in children under 2 years of age. However, the pathogenesis of Cryptosporidium infection is not well understood. In this study, we used neonatal mice and a virulent C. parvum IId subtype as an infection model to study the mechanism of diarrhea associated with cryptosporidiosis. The results showed that the C. parvum IId subtype caused intense infection and severe pathological changes. At the peak of infection, mice had reduced intestinal digestion and absorption, and increased intestinal permeability. Transcriptomic data indicated that multiple pathways were involved in regulation of C. parvum IId infection. In particular, the adherens junction and cell junction assembly were downregulated. This was further supported by the reduction of E-cadherin expression during both peak and recovery periods. These data suggest that neonatal mice infect with C. parvum experience extensive damage of the intestinal barrier, resulting in diarrhea at the peak of infection. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19352727
Volume :
18
Issue :
5
Database :
Complementary Index
Journal :
PLoS Neglected Tropical Diseases
Publication Type :
Academic Journal
Accession number :
177468073
Full Text :
https://doi.org/10.1371/journal.pntd.0012212