Development of caecaloids to study host-pathogen interactions: new insights into immunoregulatory functions of Trichuris muris extracellular vesicles in the caecum
Development of caecaloids to study host-pathogen interactions: new insights into immunoregulatory functions of Trichuris muris extracellular vesicles in the caecum
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DOI：
10.1016/j.ijpara.2020.06.001
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发表时间：
2020-08-01
影响因子：
4
通讯作者：
Berriman, Matthew
中科院分区：
文献类型：
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作者：
Duque-Correa, Maria A.;Schreiber, Fernanda;Berriman, Matthew
盲肠是小肠和大肠交界处的肠附属物，具有独特的上皮细胞，可作为包括鞭虫（鞭虫属）在内的一系列病原体的专属生态位。虽然存在从小肠（类肠）和结肠（类结肠）生长类器官的方案，但从盲肠培养类器官的条件尚未描述。在这里，我们报告的方法来生长，分化和再生小鼠成体干细胞来源的盲肠类器官，称为盲肠。我们比较了盲肠的细胞组成与肠，确定肠上皮细胞群的差异，模仿那些发现在盲肠和小肠。盲肠状体及其来源组织的肠上皮细胞组成和空间构象的显着相似性，使其能够用作体外模型来研究宿主与重要盲肠病原体的相互作用。因此，利用这个系统，我们研究了盲肠肠上皮细胞的细胞外囊泡分泌/分泌的细胞内蠕虫毛首线虫的反应。我们的研究结果揭示了鞭虫细胞外囊泡对盲肠上皮细胞的免疫调节作用，包括下调对核酸识别和I型干扰素信号的反应。(C)2020作者（S）由Elsevier Ltd代表澳大利亚寄生虫学会出版。
The caecum, an intestinal appendage in the junction of the small and large intestines, displays a unique epithelium that serves as an exclusive niche for a range of pathogens including whipworms (Trichuris spp.). While protocols to grow organoids from small intestine (enteroids) and colon (colonoids) exist, the conditions to culture organoids from the caecum have yet to be described. Here, we report methods to grow, differentiate and characterise mouse adult stem cell-derived caecal organoids, termed caecaloids. We compare the cellular composition of caecaloids with that of enteroids, identifying differences in intestinal epithelial cell populations that mimic those found in the caecum and small intestine. The remarkable similarity in the intestinal epithelial cell composition and spatial conformation of caecaloids and their tissue of origin enables their use as an in vitro model to study host interactions with important caecal pathogens. Thus, exploiting this system, we investigated the responses of caecal intestinal epithelial cells to extracellular vesicles secreted/excreted by the intracellular helminth Trichuris muris. Our findings reveal novel immunoregulatory effects of whipworm extracellular vesicles on the caecal epithelium, including the downregulation of responses to nucleic acid recognition and type-I interferon signalling. (C) 2020 The Author(s). Published by Elsevier Ltd on behalf of Australian Society for Parasitology.