Controlling Epithelial Polarity: A Human Enteroid Model for Host-Pathogen Interactions
Controlling Epithelial Polarity: A Human Enteroid Model for Host-Pathogen Interactions
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DOI：
10.1016/j.celrep.2019.01.108
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发表时间：
2019-02-26
期刊：
影响因子：
8.8
通讯作者：
Amieva, Manuel R.
中科院分区：
文献类型：
--
作者：
Co, Julia Y.;Margalef-Catala, Mar;Amieva, Manuel R.
人肠样体（源自原代胃肠道组织的上皮球体）是研究病原体与上皮相互作用的有前景的模型。然而，进入顶端肠样表面具有挑战性，因为它被封闭在球体内。我们开发了一种反转肠极性的技术，使顶端表面翻转面向介质。顶端出的小肠保持适当的极性和屏障功能，分化为主要的肠上皮细胞（IEC）类型，并表现出营养物质的极化吸收。我们使用该模型来研究宿主与病原体的相互作用，并确定了侵袭性肠病原体感染的不同极性特异性模式。肠沙门氏菌鼠伤寒血清型通过细胞骨架重排以 IEC 顶端表面为目标进行入侵，而与基底外侧受体结合的单核细胞增生李斯特氏菌则侵入细胞挤出部位的顶端表面。尽管进入方式不同，两种病原体均在顶部突出的肠样细胞内离开上皮。该模型将能够进一步检查健康和疾病方面的 IEC。
Human enteroids-epithelial spheroids derived from primary gastrointestinal tissue-are a promising model to study pathogen-epithelial interactions. However, accessing the apical enteroid surface is challenging because it is enclosed within the spheroid. We developed a technique to reverse enteroid polarity such that the apical surface everts to face the media. Apical-out enteroids maintain proper polarity and barrier function, differentiate into the major intestinal epithelial cell (IEC) types, and exhibit polarized absorption of nutrients. We used this model to study host-pathogen interactions and identified distinct polarity-specific patterns of infection by invasive enteropathogens. Salmonella enterica serovar Typhimurium targets IEC apical surfaces for invasion via cytoskeletal rearrangements, and Listeria monocytogenes, which binds to basolateral receptors, invade apical surfaces at sites of cell extrusion. Despite different modes of entry, both pathogens exit the epithelium within apically extruding enteroid cells. This model will enable further examination of IECs in health and disease.