Modelling Cryptosporidium infection in human small intestinal and lung organoids

Inha Heo, Devanjali Dutta, Deborah A. Schaefer, Nino Iakobachvili, Benedetta Artegiani, Norman Sachs, Kim E. Boonekamp, Gregory Bowden, Antoni P.A. Hendrickx, Robert J.L. Willems, Peter J. Peters, Michael W. Riggs, Roberta O'Connor, Hans Clevers

Research output: Contribution to journalArticle

70 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)814-823
Number of pages10
JournalNature Microbiology
Volume3
Issue number7
DOIs
StatePublished - Jul 1 2018

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

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    Heo, I., Dutta, D., Schaefer, D. A., Iakobachvili, N., Artegiani, B., Sachs, N., Boonekamp, K. E., Bowden, G., Hendrickx, A. P. A., Willems, R. J. L., Peters, P. J., Riggs, M. W., O'Connor, R., & Clevers, H. (2018). Modelling Cryptosporidium infection in human small intestinal and lung organoids. Nature Microbiology, 3(7), 814-823. https://doi.org/10.1038/s41564-018-0177-8