Modelling Cryptosporidium infection in human small intestinal and lung organoids

被引:293
作者
Heo, Inha [1 ]
Dutta, Devanjali [1 ]
Schaefer, Deborah A. [2 ]
Iakobachvili, Nino [3 ]
Artegiani, Benedetta [1 ]
Sachs, Norman [1 ]
Boonekamp, Kim E. [1 ]
Bowden, Gregory [4 ]
Hendrickx, Antoni P. A. [5 ]
Willems, Robert J. L. [5 ]
Peters, Peter J. [3 ]
Riggs, Michael W. [2 ]
O'Connor, Roberta [4 ]
Clevers, Hans [1 ,6 ]
机构
[1] UMC Utrecht, Royal Netherlands Acad Arts & Sci KNAW, Oncode Inst, Hubrecht Inst, Utrecht, Netherlands
[2] Univ Arizona, Coll Agr & Life Sci, Sch Anim & Comparat Biomed Sci, Tucson, AZ USA
[3] Maastricht Univ, Maastricht Multimodal Mol Imaging Inst M4I, Maastricht, Netherlands
[4] Washington State Univ, Coll Vet Med, Vet Microbiol & Pathol, Pullman, WA 99164 USA
[5] Univ Med Ctr Utrecht, Dept Med Microbiol, Utrecht, Netherlands
[6] Princess Maxima Ctr, Utrecht, Netherlands
基金
欧洲研究理事会;
关键词
ELECTRON-MICROSCOPIC OBSERVATION; LISTERIA-MONOCYTOGENES; ZAMBIAN CHILDREN; PARVUM; INFECTION; DISEASE; CRYPTOSPORIDIOSIS; APICOMPLEXA; MORTALITY; EVOLUTION;
D O I
10.1038/s41564-018-0177-8
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
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.
引用
收藏
页码:814 / +
页数:15
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