Bioengineered Human Organ-on-Chip Reveals Intestinal Microenvironment and Mechanical Forces Impacting Shigella Infection
Bioengineered Human Organ-on-Chip Reveals Intestinal Microenvironment and Mechanical Forces Impacting Shigella Infection
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DOI：
10.1016/j.chom.2019.09.007
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发表时间：
2019-09-11
影响因子：
30.3
通讯作者：
Sauvonnet, Nathalie
中科院分区：
文献类型：
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作者：
Grassart, Alexandre;Malarde, Valerie;Sauvonnet, Nathalie
肠道上皮细胞经常暴露在病原体和机械力之下。但是，机械力的影响会导致感染导致腹泻！疾病在很大程度上仍不为人所知。在这里，我们使用肠芯片技术研究了流动和蠕动是否影响3D结肠上皮内人类病原体志贺氏菌的传染性。引人注目的是，感染显著增加，最低限度的细菌负荷足以从顶端入侵肠细胞，并引发屏障完整性的丧失，从而改变了有关志贺氏菌早期入侵的范式。志贺氏菌迅速定植上皮样隐窝状凹陷，并展示了微环境的基本作用。此外，通过调节微环境的机械力，我们发现蠕动影响志贺氏菌的入侵。总而言之，我们的结果表明，志贺菌通过利用微结构和机械力有效地入侵肠道，从而利用肠道微环境。这种方法将使对人类限制的肠道病原体的分子和机械讯问成为可能。
Intestinal epithelial cells are constantly exposed to pathogens and mechanical forces. However, the impact of mechanical forces on infections leading to diarrhea! diseases remains largely unknown. Here, we addressed whether flow and peristalsis impact the infectivity of the human pathogen Shigella within a 3D colonic epithelium using Intestine-Chip technology. Strikingly, infection is significantly increased and minimal bacterial loads are sufficient to invade enterocytes from the apical side and trigger loss of barrier integrity, thereby shifting the paradigm about early stage Shigella invasion. Shigella quickly colonizes epithelial crypt-like invaginations and demonstrates the essential role of the microenvironment. Furthermore, by modulating the mechanical forces of the microenvironment, we find that peristalsis impacts Shigella invasion. Collectively, our results reveal that Shigella leverages the intestinal microenvironment by taking advantage of the micro-architecture and mechanical forces to efficiently invade the intestine. This approach will enable molecular and mechanistic interrogation of human-restricted enteric pathogens.