RT Journal Article SR Electronic T1 Development of caecaloids to study host-pathogen interactions: new insights into immunoregulatory functions of Trichuris muris extracellular vesicles in the caecum JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.05.11.087684 DO 10.1101/2020.05.11.087684 A1 María A. Duque-Correa A1 Fernanda Schreiber A1 Faye H. Rodgers A1 David Goulding A1 Sally Forrest A1 Ruby White A1 Amy Buck A1 Richard K. Grencis A1 Matthew Berriman YR 2020 UL http://biorxiv.org/content/early/2020/05/12/2020.05.11.087684.abstract AB The caecum, an intestinal appendage in the junction of the small and large intestines, displays a unique epithelium that serves as an exclusive niche for a range of pathogens including whipworms (Trichuris spp). While protocols to grow organoids from small intestine (enteroids) and colon (colonoids) exist, the conditions to culture organoids from the caecum have yet to be described. Here, we report methods to grow, differentiate and characterise mouse adult stem cell-derived caecal organoids, termed caecaloids. We compare the cellular composition of caecaloids to that of enteroids identifying differences in intestinal epithelial cell (IEC) populations that mimic those found in the caecum and small intestine. The remarkable similarity in the IECs composition and spatial conformation of caecaloids and their tissue of origin enables their use as an in vitro model to study host interactions with important caecal pathogens. Thus, exploiting this system we investigated the responses of caecal IECs to extracellular vesicles (EVs) secreted/excreted by the intracellular helminth Trichuris muris. Our findings reveal novel immunoregulatory effects of whipworm EVs on the caecal epithelium, including the downregulation of responses to nucleic acid recognition and type-I interferon (IFN) signalling.Competing Interest StatementThe authors have declared no competing interest.