Modelling Cryptosporidium infection in human small intestinal and lung organoids

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.

Long‐term expanding human airway organoids for disease modeling

“…Tumors show features of adenocarcinomas (HE stainings) and are integrated within murine stroma (human keratin immunolabeling). Validating the robustness of AOs as model for human pulmonary infections are recent studies with enterovirus (van der Sanden et al, 2018), influenza virus (Hui et al, 2018;Zhou et al, 2018), and cryptosporidium (Heo et al, 2018). C WGS reveals largely conserved mutation status of lung cancer genes between matched tumor-organoid pairs (left plot, Appendix Table S1).…”

A One Health Approach to Tackle Cryptosporidiosis

“…Recently, there has been some exciting progress on the in vitro culture of Cryptosporidium parasites using hollow-fibre technology [71] and the demonstration of the complete life cycle of C. parvum when cultured in human and mouse intestinal organoids [72,73]. Heo et al microinjected Cryptosporidium into the lumen of three-dimensional human-derived organoids [72], while Wilke et al infected monolayers of mouse-derived organoids cultured at an air-liquid interface in transwells [73]. Both culture systems support long-term growth (N20 days) and produce viable, infectious oocysts.…”

Organoids – New Models for Host–Helminth Interactions

“…In particular, Toxoplasma gondii infects bovine and porcine small intestinal organoids [31]. Furthermore, the entire life cycle of Cryptosporidium parvum can now be modelled in murine and human small intestinal [33,34] and lung organoids [34]. Lung organoids have successfully recapitulated respiratory tract infections with C. parvum occurring in immune-competent and -deficient individuals [34].…”

“…For pathogens other than helminths, there are no reports on the impact of the dimensional conformation and architecture of organoids on the interactions with the host cells. Indeed, the life cycle of the protozoan parasite C. parvum can be replicated both in 3D and 2D organoids [33,34].…”