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Nat Microbiol. 2018 Jul;3(7):814-823. doi: 10.1038/s41564-018-0177-8. Epub 2018 Jun 25.

Modelling Cryptosporidium infection in human small intestinal and lung organoids.

Author information

1
Hubrecht Institute, Oncode Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), UMC Utrecht, Utrecht, The Netherlands.
2
School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, AZ, USA.
3
The Maastricht Multimodal Molecular Imaging Institute (M4I), Maastricht University, Maastricht, The Netherlands.
4
Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA.
5
Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
6
Veterinary Microbiology and Pathology, College of Veterinary Medicine, Washington State University, Pullman, WA, USA. rob.oconnor@wsu.edu.
7
Hubrecht Institute, Oncode Institute, Royal Netherlands Academy of Arts and Sciences (KNAW), UMC Utrecht, Utrecht, The Netherlands. h.clevers@hubrecht.eu.
8
Princess Máxima Centre, Utrecht, The Netherlands. h.clevers@hubrecht.eu.

Abstract

Stem-cell-derived organoids recapitulate in vivo physiology of their original tissues, representing valuable systems to model medical disorders such as infectious diseases. Cryptosporidium, a protozoan parasite, is a leading cause of diarrhoea and a major cause of child mortality worldwide. Drug development requires detailed knowledge of the pathophysiology of Cryptosporidium, but experimental approaches have been hindered by the lack of an optimal in vitro culture system. Here, we show that Cryptosporidium can infect epithelial organoids derived from human small intestine and lung. The parasite propagates within the organoids and completes its complex life cycle. Temporal analysis of the Cryptosporidium transcriptome during organoid infection reveals dynamic regulation of transcripts related to its life cycle. Our study presents organoids as a physiologically relevant in vitro model system to study Cryptosporidium infection.

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PMID:
29946163
PMCID:
PMC6027984
DOI:
10.1038/s41564-018-0177-8
[Indexed for MEDLINE]
Free PMC Article

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