A productive immunocompetent mouse model of cryptosporidiosis with long oocyst shedding duration for immunological studies

0558790 - BC 2023 RIV GB eng J - Journal Article
He, X. - Huang, W. - Sun, L. - Hou, T. - Wan, Z. - Li, N. - Guo, Y. - Kváč, Martin - Xiao, L. - Feng, Y.
A productive immunocompetent mouse model of cryptosporidiosis with long oocyst shedding duration for immunological studies.
Journal of Infection. Roč. 84, č. 5 (2022), s. 710-721. ISSN 0163-4453. E-ISSN 1532-2742
Institutional support: RVO:60077344
Keywords : intestinal epithelial-cells * innate immune-responses * global burden * parvum * infection * gene * mice * delivery * subtype * tyzzeri * Cryptosporidium * Cryptosporidiosis * Animal model * c57bl * 6J mice * Immune responses * ?defensins
OECD category: Infectious Diseases
Impact factor: 28.2, year: 2022
Method of publishing: Limited access
https://onlinelibrary.wiley.com/doi/10.1002/bies.202100258

Objectives: Studies on the pathogenesis and immune responses of Cryptosporidium infection and development of drugs and vaccines use mostly immunocompromised mouse models. In this study, we establish an immunocompetent mouse model of cryptosporidiosis with high intensity and long duration of infection. Methods: We have obtained a Cryptosporidium tyzzeri isolate from laboratory mice, and infect adult C57BL/6 J mice experimentally with the isolate for determinations of infectivity, infection patterns, pathological changes, and transcriptomic responses. Results: The isolate has an ID 50 of 5.2 oocysts, with oocyst shedding lasting at high levels for > 2 months. The oocyst shedding is boosted by immunosuppression of animals and suppressed by paromomycin treatment. The isolate induces strong inflammatory and acquired immune responses, but down-regulates the expression of alpha-defensins in epithelium. Comparative genomics analysis has revealed significant sequence differences from other isolates in subtelomeric genes. The down-regulation of the expression of alpha-defensins may be responsible for the high-intensity and long-lasting infection in this animal model. Conclusions: The immunocompetent mouse model of cryptosporidiosis developed has the advantages of high oocyst shedding intensity and long oocyst shedding duration. It provides an effective mechanism for the propagation of Cryptosporidium , evaluations of potential therapeutics, and studies of pathogen biology and immune responses. (c) 2022 The British Infection Association. Published by Elsevier Ltd. All rights reserved.
Permanent Link: https://hdl.handle.net/11104/0339077