Cryptosporidium infection of human small intestinal epithelial cells induces type III interferon and impairs infectivity of Rotavirus.

Cryptosporidium infection of human small intestinal epithelial cells induces type III interferon and impairs infectivity of Rotavirus.
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DOI:
10.1080/19490976.2023.2297897
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发表时间:
2024-01
期刊:
影响因子:
12.2
通讯作者:
--
中科院分区:
医学2区
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--
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隐孢子虫病是资源贫乏环境中婴儿严重腹泻的主要原因。大多数感染是由人类特异性病原体C引起的。人和缺乏体外生长平台限制了我们对宿主-病原体相互作用的理解和有效治疗的发展。为了解决这个问题,我们开发了一个干细胞衍生的培养系统,用于C。使用在气液界面(ALI)条件下分化的人肠细胞的人。人ALI培养物支持C.包括所有生命周期阶段的体外人。隐孢子虫感染诱导肠上皮细胞产生强烈的干扰素反应,这可能部分是由寄生虫中的内源性dsRNA病毒驱动的。先前感染隐孢子虫诱导III型IFN分泌,从而钝化轮状病毒感染,包括减毒活疫苗株。hALI的开发为进一步研究人类特异性病原体提供了平台,包括可能改变疫苗效力的临床重要合并感染。
Cryptosporidiosis is a major cause of severe diarrheal disease in infants from resource poor settings. The majority of infections are caused by the human-specific pathogen C. hominis and absence of in vitro growth platforms has limited our understanding of host-pathogen interactions and development of effective treatments. To address this problem, we developed a stem cell-derived culture system for C. hominis using human enterocytes differentiated under air-liquid interface (ALI) conditions. Human ALI cultures supported robust growth and complete development of C. hominis in vitro including all life cycle stages. Cryptosporidium infection induced a strong interferon response from enterocytes, possibly driven, in part, by an endogenous dsRNA virus in the parasite. Prior infection with Cryptosporidium induced type III IFN secretion and consequently blunted infection with Rotavirus, including live attenuated vaccine strains. The development of hALI provides a platform for further studies on human-specific pathogens, including clinically important coinfections that may alter vaccine efficacy.
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