Authors

D Smith¹;  ¹ Moredun Research Institute, UK

Discussion

Organoids are stem cell-derived organized multicellular structures that mimic a specific tissue type. In recent years, we have shown that primary organoids derived from gastrointestinal tissue in ruminants are tissue-, species- and even individual animal-specific. In a recent study, this latter point inspired us to determine whether organoids derived from hyper-immune animals infected with a gastrointestinal nematode retained an epigenetic “blueprint” of infection/immune status. Here, we report that duodenal organoids derived from longitudinally Trichostrongylus colubriformis trickle-challenged sheep have a distinctly different gene expression profile compared to organoids derived from healthy animals, after multiple organoid passages in a parasite-free environment. Our results indicate that T. colubriformis infection has a reprogramming effect on the host that diminishes intestinal cell differentiation and gut motility and alters immune signaling. Moreover, gene expression of known markers of resistance are also increased in organoids derived from hyper-immune animals, despite multiple rounds of passaging in a worm-free environment. We have now established organoid cultures from diverse tissue types and across various large animal species and we are now applying these tissue culture systems to model a range of host:pathogens interactions and vaccine delivery systems in the lab.