Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China; Guangdong Laboratory for Lingnan Modern Agriculture. Guangzhou, Guangdong 510642, China.
Center for Emerging and Zoonotic Diseases, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
J Infect. 2022 May;84(5):710-721. doi: 10.1016/j.jinf.2022.02.019. Epub 2022 Feb 19.
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.
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.
The isolate has an ID 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 α-defensins in epithelium. Comparative genomics analysis has revealed significant sequence differences from other isolates in subtelomeric genes. The down-regulation of the expression of α-defensins may be responsible for the high-intensity and long-lasting infection in this animal model.
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.
研究隐孢子虫感染的发病机制和免疫反应以及药物和疫苗的开发，大多使用免疫功能低下的小鼠模型。本研究建立了一种高强度、长时间感染的免疫功能正常的隐孢子虫感染小鼠模型。
我们从实验室小鼠中获得了一株隐孢子虫 Tyzeri 分离株，并通过实验感染成年 C57BL/6J 小鼠，以确定感染性、感染模式、病理变化和转录组反应。
该分离株的 ID 为 5.2 个卵囊，卵囊脱落水平持续高水平>2 个月。动物免疫抑制可增强卵囊脱落，而巴龙霉素治疗可抑制卵囊脱落。该分离株诱导强烈的炎症和获得性免疫反应，但下调上皮细胞中α-防御素的表达。比较基因组学分析显示，在端粒基因附近的基因上与其他分离株存在显著的序列差异。α-防御素表达的下调可能是该动物模型高强度和长时间感染的原因。
本研究开发的免疫功能正常的隐孢子虫感染小鼠模型具有高卵囊脱落强度和长卵囊脱落持续时间的优点。它为隐孢子虫的繁殖、潜在治疗药物的评估以及病原体生物学和免疫反应的研究提供了有效的机制。
