Tissue atlas of neonatal calf cryptosporidiosis reveals high levels of infection throughout the intestinal tract

Cryptosporidium parvum is an important parasite that causes cryptosporidiosis, a devastating and potentially deadly diarrhoeal disease. C. parvum is zoonotic, infecting humans and farm animals (most commonly, cattle and sheep). Bovine cryptosporidiosis is of a particularly high concern due to the significant economic impact to agriculture, caused even by non-fatal cases. For both humans and animals, current treatments are extremely limited and ineffective in the most at-risk groups, meaning there is an urgent need to develop new anti-cryptosporidials. However, this development is hindered by a lack of understanding of host-parasite interaction. Many critical knowledge gaps currently exist; the most fundamental of which being the location of the parasite within the gut of the natural host. Until the present study, this was hypothesised to be the ileo-caecal junction, however this has never been experimentally evidenced. With a lack of simple in vitro culture systems that support the entire Cryptosporidium life cycle, our current understanding of its biology has been developed from in vivo studies in immunocompromised mice. However, it is unclear how well these recapitulate infection in the natural host. To address this, we established an acute, moderate experimental C. parvum infection in neonatal. Using transgenic parasites, we mapped and quantified infection throughout the neonatal calf gut to appreciate the true breadth of infection in this host for the first time. We also mapped infection in the same way in two immunocompromised mouse models to draw robust comparisons between the mouse and neonatal calf as models of host-parasite interaction.