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Defining the early stages of intestinal colonisation by whipworms.

Title: Defining the early stages of intestinal colonisation by whipworms.
Authors: Duque-Correa, María A; Goulding, David; Rodgers, Faye H; Gillis, J Andrew; Cormie, Claire; Rawlinson, Kate A; Bancroft, Allison J; Bennett, Hayley M; Lotkowska, Magda E; Reid, Adam J; Speak, Anneliese O; Scott, Paul; Redshaw, Nicholas; Tolley, Charlotte; McCarthy, Catherine; Brandt, Cordelia; Sharpe, Catherine; Ridley, Caroline; Moya, Judit Gali; Carneiro, Claudia M; Starborg, Tobias; Hayes, Kelly S; Holroyd, Nancy; Sanders, Mandy; Thornton, David J; Grencis, Richard K; Berriman, Matthew
Source: nlmid: 101528555 ; essn: 2041-1723
Publisher Information: Springer Nature; //doi.org/10.1038/s41467-022-29334-0
Publication Year: 2022
Collection: Apollo - University of Cambridge Repository
Subject Terms: Animals; Helminths; Intestinal Mucosa; Intestines; Mammals; Mice; Trichuriasis; Trichuris
Description: Whipworms are large metazoan parasites that inhabit multi-intracellular epithelial tunnels in the large intestine of their hosts, causing chronic disease in humans and other mammals. How first-stage larvae invade host epithelia and establish infection remains unclear. Here we investigate early infection events using both Trichuris muris infections of mice and murine caecaloids, the first in-vitro system for whipworm infection and organoid model for live helminths. We show that larvae degrade mucus layers to access epithelial cells. In early syncytial tunnels, larvae are completely intracellular, woven through multiple live dividing cells. Using single-cell RNA sequencing of infected mouse caecum, we reveal that progression of infection results in cell damage and an expansion of enterocytes expressing of Isg15, potentially instigating the host immune response to the whipworm and tissue repair. Our results unravel intestinal epithelium invasion by whipworms and reveal specific host-parasite interactions that allow the whipworm to establish its multi-intracellular niche.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
Relation: PMC8976045; https://www.repository.cam.ac.uk/handle/1810/336816
DOI: 10.17863/CAM.84235
Availability: https://www.repository.cam.ac.uk/handle/1810/336816; https://doi.org/10.17863/CAM.84235
Rights: Attribution 4.0 International ; https://creativecommons.org/licenses/by/4.0/
Accession Number: edsbas.479959A9
Database: BASE