Heo, I. et al. Nat. Microbiol. 3, 814–823 (2018).

Disease modeling can be difficult with obligate parasites because of their complex life cycle requirements. The parasite Cryptosporidium is responsible for a potentially fatal diarrheal disease known as cryptosporidiosis, which takes a significant toll on the health of infants in developing countries. Heo et al. show that small intestinal and lung organoids derived from healthy human donors can be used as models for Cryptosporidium infection. Differentiated intestinal organoids microinjected with oocysts supported the entire life cycle of the parasite in long-term and serial infections. Organoids cultured under conditions that produce less differentiation are less susceptible to infection. Bronchial airway organoids also support infection, thus allowing closer inspection of the poorly studied lung epithelial infection route. These new models will help to unravel Cryptosporidium biology and cell–microbe interactions.