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dc.contributor.authorDuque-Correa, María A
dc.contributor.authorGoulding, David
dc.contributor.authorRodgers, Faye H
dc.contributor.authorGillis, J Andrew
dc.contributor.authorCormie, Claire
dc.contributor.authorRawlinson, Kate A
dc.contributor.authorBancroft, Allison J
dc.contributor.authorBennett, Hayley M
dc.contributor.authorLotkowska, Magda E
dc.contributor.authorReid, Adam J
dc.contributor.authorSpeak, Anneliese O
dc.contributor.authorScott, Paul
dc.contributor.authorRedshaw, Nicholas
dc.contributor.authorTolley, Charlotte
dc.contributor.authorMcCarthy, Catherine
dc.contributor.authorBrandt, Cordelia
dc.contributor.authorSharpe, Catherine
dc.contributor.authorRidley, Caroline
dc.contributor.authorMoya, Judit Gali
dc.contributor.authorCarneiro, Claudia M
dc.contributor.authorStarborg, Tobias
dc.contributor.authorHayes, Kelly S
dc.contributor.authorHolroyd, Nancy
dc.contributor.authorSanders, Mandy
dc.contributor.authorThornton, David J
dc.contributor.authorGrencis, Richard K
dc.contributor.authorBerriman, Matthew
dc.date.accessioned2022-05-09T09:10:54Z
dc.date.available2022-05-09T09:10:54Z
dc.date.issued2022-04-01
dc.identifier.issn2041-1723
dc.identifier.other35365634
dc.identifier.otherPMC8976045
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336816
dc.description.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.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101528555
dc.sourceessn: 2041-1723
dc.subjectIntestines
dc.subjectIntestinal Mucosa
dc.subjectAnimals
dc.subjectMammals
dc.subjectMice
dc.subjectHelminths
dc.subjectTrichuris
dc.subjectTrichuriasis
dc.titleDefining the early stages of intestinal colonisation by whipworms.
dc.typeArticle
dc.date.updated2022-05-09T09:10:54Z
prism.issueIdentifier1
prism.publicationNameNat Commun
prism.volume13
dc.identifier.doi10.17863/CAM.84235
dcterms.dateAccepted2022-03-08
rioxxterms.versionofrecord10.1038/s41467-022-29334-0
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidDuque-Correa, María A [0000-0002-0567-0412]
dc.contributor.orcidRawlinson, Kate A [0000-0001-8297-8405]
dc.contributor.orcidBennett, Hayley M [0000-0001-8879-2855]
dc.contributor.orcidReid, Adam J [0000-0002-5926-7768]
dc.contributor.orcidSpeak, Anneliese O [0000-0003-4890-4685]
dc.contributor.orcidTolley, Charlotte [0000-0002-1119-7983]
dc.contributor.orcidCarneiro, Claudia M [0000-0002-6002-857X]
dc.contributor.orcidHayes, Kelly S [0000-0003-3034-048X]
dc.contributor.orcidThornton, David J [0000-0001-7148-1970]
dc.contributor.orcidGrencis, Richard K [0000-0002-7592-0085]
dc.contributor.orcidBerriman, Matthew [0000-0002-9581-0377]
dc.identifier.eissn2041-1723
pubs.funder-project-idWellcome Trust (206194, Z10661/Z/18/Z, 088785/Z/09/Z)
pubs.funder-project-idNational Centre for the Replacement, Refinement and Reduction of Animals in Research (NC/P001521/1)
cam.issuedOnline2022-04


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International