Bioengineered Human Organ-on-Chip Reveals Intestinal Microenvironment and Mechanical Forces Impacting Shigella Infection

Intestinal epithelial cells are constantly exposed to pathogens and mechanical forces. However, the impact of mechanical forces on infections leading to diarrheal diseases remains largely unknown. Here, we addressed whether flow and peristalsis impact the infectivity of the human pathogen Shigella w...

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Bibliographic Details
Published in:Cell host & microbe 2019-10, Vol.26 (4), p.565-565
Main Authors: Grassart, Alexandre, Malardé, Valérie, Gobaa, Samy, Sartori-Rupp, Anna, Kerns, Jordan, Karalis, Katia, Marteyn, Benoit, Sansonetti, Philippe, Sauvonnet, Nathalie
Format: Article
Language:English
Subjects:
Bacterial Adhesion
Bioengineering
Biomaterials
Caco-2 Cells
Cellular Biology
Dysentery, Bacillary
Enterocytes
Epithelial Cells
Host-Pathogen Interactions
Humans
Intestinal Mucosa
Intestines
Life Sciences
Microbiology and Parasitology
Shigella
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Summary:Intestinal epithelial cells are constantly exposed to pathogens and mechanical forces. However, the impact of mechanical forces on infections leading to diarrheal 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 microarchitecture and mechanical forces to efficiently invade the intestine. This approach will enable molecular and mechanistic interrogation of human-restricted enteric pathogens.
ISSN:1931-3128
1934-6069
DOI:10.1016/j.chom.2019.09.007