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

doi:10.1038/s41564-018-0177-8

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 journal › Article › peer-review

289 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 language	English (US)
Pages (from-to)	814-823
Number of pages	10
Journal	Nature Microbiology
Volume	3
Issue number	7
DOIs	https://doi.org/10.1038/s41564-018-0177-8
State	Published - Jul 1 2018
Externally published	Yes

Bibliographical note

Funding Information:
We are grateful to A.A. Arias, J. Puschhof and H. Hu for assistance with mapping of RNA sequencing data; the Franceschi Microscopy and Imaging Center and D.L. Mullendore at Washington State University for TEM preparation and imaging of isolated organoid oocysts; and C. Joo, J. Beumer and O. Kopper for discussions and critical reading of the manuscript. I.H. is the recipient of a VENI grant from the Netherlands Organization for Scientific Research (NWO-ALW, 863.14.002) and was supported by Marie Curie fellowships from the European Commission (Proposal 330571 FP7-PEOPLE-2012-IIF). D.D. is the recipient of a VENI grant from the Netherlands Organization for Scientific Research (NWO-ALW, 016.Veni.171.015). The research leading to these results has received funding from the European Research Council under ERC Advanced Grant Agreement no. 67013 and from NIH NIAIH under R21 AT009174. This work is part of the Oncode Institute, which is partly financed by the Dutch Cancer Society and was funded by a grant from the Dutch Cancer Society.

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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

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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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note = "Funding Information: We are grateful to A.A. Arias, J. Puschhof and H. Hu for assistance with mapping of RNA sequencing data; the Franceschi Microscopy and Imaging Center and D.L. Mullendore at Washington State University for TEM preparation and imaging of isolated organoid oocysts; and C. Joo, J. Beumer and O. Kopper for discussions and critical reading of the manuscript. I.H. is the recipient of a VENI grant from the Netherlands Organization for Scientific Research (NWO-ALW, 863.14.002) and was supported by Marie Curie fellowships from the European Commission (Proposal 330571 FP7-PEOPLE-2012-IIF). D.D. is the recipient of a VENI grant from the Netherlands Organization for Scientific Research (NWO-ALW, 016.Veni.171.015). The research leading to these results has received funding from the European Research Council under ERC Advanced Grant Agreement no. 67013 and from NIH NIAIH under R21 AT009174. This work is part of the Oncode Institute, which is partly financed by the Dutch Cancer Society and was funded by a grant from the Dutch Cancer Society. Publisher Copyright: {\textcopyright} 2018 The Author(s).",

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AU - Heo, Inha

AU - Dutta, Devanjali

AU - Schaefer, Deborah A.

AU - Iakobachvili, Nino

AU - Artegiani, Benedetta

AU - Sachs, Norman

AU - Boonekamp, Kim E.

AU - Bowden, Gregory

AU - Hendrickx, Antoni P.A.

AU - Willems, Robert J.L.

AU - Peters, Peter J.

AU - Riggs, Michael W.

AU - O'Connor, Roberta

AU - Clevers, Hans

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Modelling Cryptosporidium infection in human small intestinal and lung organoids

Abstract

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