Defining the early stages of intestinal colonisation by whipworms.
Defining the early stages of intestinal colonisation by whipworms.
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DOI：
10.1038/s41467-022-29334-0
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发表时间：
2022-04-01
影响因子：
16.6
通讯作者：
Berriman M
中科院分区：
文献类型：
--
作者：
Duque-Correa MA;Goulding D;Rodgers FH;Gillis JA;Cormie C;Rawlinson KA;Bancroft AJ;Bennett HM;Lotkowska ME;Reid AJ;Speak AO;Scott P;Redshaw N;Tolley C;McCarthy C;Brandt C;Sharpe C;Ridley C;Moya JG;Carneiro CM;Starborg T;Hayes KS;Holroyd N;Sanders M;Thornton DJ;Grencis RK;Berriman M
鞭虫是大型后生动物寄生虫，栖息在其宿主大肠中的多细胞内上皮隧道中，导致人类和其他哺乳动物的慢性疾病。第一阶段幼虫如何侵入宿主上皮细胞并建立感染仍不清楚。在这里，我们调查使用鞭虫感染的小鼠和小鼠盲肠，鞭虫感染和活蠕虫类器官模型的第一个体外系统的早期感染事件。我们发现，幼虫降解粘液层进入上皮细胞。在早期的合胞体隧道中，幼虫完全是细胞内的，通过多个活的分裂细胞编织。使用单细胞RNA测序感染的小鼠盲肠，我们发现，感染的进展导致细胞损伤和扩张的肠上皮细胞表达的Isg 15，潜在地煽动宿主免疫反应的鞭虫和组织修复。我们的研究结果解开肠上皮入侵鞭虫，并揭示特定的宿主-寄生虫的相互作用，使鞭虫建立其多细胞内的生态位。鞭虫是引起人类和其他哺乳动物慢性疾病的大型寄生虫。在这里，作者展示了幼虫如何在肠道内壁形成隧道，并揭示了小鼠和小鼠盲肠中通过Isg 15感染的早期宿主反应。
Whipworms are large metazoan parasites that inhabit multi-intracellular epithelial tunnels in the large intestine of their hosts, causing chronic disease in humans and other mammals. How first-stage larvae invade host epithelia and establish infection remains unclear. Here we investigate early infection events using both Trichuris muris infections of mice and murine caecaloids, the first in-vitro system for whipworm infection and organoid model for live helminths. We show that larvae degrade mucus layers to access epithelial cells. In early syncytial tunnels, larvae are completely intracellular, woven through multiple live dividing cells. Using single-cell RNA sequencing of infected mouse caecum, we reveal that progression of infection results in cell damage and an expansion of enterocytes expressing of Isg15, potentially instigating the host immune response to the whipworm and tissue repair. Our results unravel intestinal epithelium invasion by whipworms and reveal specific host-parasite interactions that allow the whipworm to establish its multi-intracellular niche. Whipworms are large parasites causing chronic disease in humans and other mammals. Here, the authors show how larvae create tunnels inside the gut lining and reveal the early host response to infection via Isg15 in mice and murine caecaloids.
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DOI：
10.1038/s41577-020-0301-x
发表时间：
2020-10
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
7.7
作者：
Criswell, Katharine E.;Gillis, J. Andrew
通讯作者：
Gillis, J. Andrew
影响因子：
15.9
作者：
CHADEE, K;PETRI, WA;RAVDIN, JI
通讯作者：
RAVDIN, JI
影响因子：
4.4
作者：
Iglesias-Guimarais, Victoria;Ahrends, Tomasz;Borst, Jannie
通讯作者：
Borst, Jannie
影响因子：
4
作者：
Duque-Correa, Maria A.;Schreiber, Fernanda;Berriman, Matthew
通讯作者：
Berriman, Matthew