Genetically tractable rodent models for Cryptosporidium hominis and C. parvum infections: identifying differences in infection sites between host species.

Cryptosporidiosis causes severe diarrhea in children and livestock. However, the absence of suitable rodent models has led to a lack of effective drugs and vaccines. In this study, genetically tractable rat and mouse models were developed for the two main causes of human cryptosporidiosis: Cryptosporidium hominis and C. parvum. Neonatal mice and rats were successfully infected with two nonhuman primate-adapted C. hominis isolates and one C. parvum IId isolate, resulting in high oocyst shedding. Using isolates tagged with fluorescent proteins and luciferases enabled the easy detection and quantification of oocyst shedding. Both Cryptosporidium species primarily infected the ileum, cecum, and colon of neonatal mice. In contrast, the parasites primarily colonized the duodenum and jejunum of neonatal rats. Both species responded to treatment with a lysyl-tRNA synthetase inhibitor in the rat model. Developing tractable animal models with different infection sites will allow for comparative studies of the biology and immunity of major human-pathogenic Cryptosporidium species, as well as the evaluation of potential drugs and vaccines.