Defining the early stages of intestinal colonisation by whipworms
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Published:2022-04-01
Issue:1
Volume:13
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Duque-Correa María A.ORCID, Goulding David, Rodgers Faye H., Gillis J. Andrew, Cormie Claire, Rawlinson Kate A.ORCID, Bancroft Allison J., Bennett Hayley M.ORCID, Lotkowska Magda E., Reid Adam J.ORCID, Speak Anneliese O.ORCID, Scott Paul, Redshaw Nicholas, Tolley CharlotteORCID, McCarthy Catherine, Brandt Cordelia, Sharpe Catherine, Ridley Caroline, Moya Judit Gali, Carneiro Claudia M.ORCID, Starborg Tobias, Hayes Kelly S.ORCID, Holroyd Nancy, Sanders Mandy, Thornton David J.ORCID, Grencis Richard K.ORCID, Berriman MatthewORCID
Abstract
AbstractWhipworms 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.
Funder
Wellcome Trust National Centre for the Replacement Refinement and Reduction of Animals in Research
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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