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dc.contributor.authorDuque-Correa, María Aen
dc.contributor.authorKarp, Natasha Aen
dc.contributor.authorMcCarthy, Catherineen
dc.contributor.authorForman, Simonen
dc.contributor.authorGoulding, Daviden
dc.contributor.authorSankaranarayanan, Geethaen
dc.contributor.authorJenkins, Timothyen
dc.contributor.authorReid, Adam Jen
dc.contributor.authorCambridge, Emma Len
dc.contributor.authorBallesteros Reviriego, Carmenen
dc.contributor.authorSanger Mouse Genetics Project,en
dc.contributor.author3i consortium,en
dc.contributor.authorMüller, Werneren
dc.contributor.authorCantacessi, Cinziaen
dc.contributor.authorDougan, Gordonen
dc.contributor.authorGrencis, Richard Ken
dc.contributor.authorBerriman, Matthewen
dc.date.accessioned2019-01-22T00:31:37Z
dc.date.available2019-01-22T00:31:37Z
dc.date.issued2019-01-14en
dc.identifier.issn1553-7366
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/288327
dc.description.abstractThe whipworm Trichuris trichiura is a soil-transmitted helminth that dwells in the epithelium of the caecum and proximal colon of their hosts causing the human disease, trichuriasis. Trichuriasis is characterized by colitis attributed to the inflammatory response elicited by the parasite while tunnelling through intestinal epithelial cells (IECs). The IL-10 family of receptors, comprising combinations of subunits IL-10R, IL-10R, IL-22R and IL-28R, modulates intestinal inflammatory responses. Here we carefully dissected the role of these subunits in the resistance of mice to infection with T. muris, a mouse model of the human whipworm T. trichiura. Our findings demonstrate that whilst IL-22R and IL-28R are dispensable in the host response to whipworms, IL-10 signalling through IL-10R and IL-10R is essential to control caecal pathology, worm expulsion and survival during T. muris infections. We show that deficiency of IL-10, IL-10R and IL-10R results in dysbiosis of the caecal microbiota characterised by expanded populations of opportunistic bacteria of the families Enterococcaceae and Enterobacteriaceae. Moreover, breakdown of the epithelial barrier after whipworm infection in IL-10, IL-10R and IL-10R-deficient mice, allows the translocation of these opportunistic pathogens or their excretory products to the liver causing organ failure and lethal disease. Importantly, bone marrow chimera experiments indicate that signalling through IL-10R and IL-10R in haematopoietic cells, but not IECs, is crucial to control worm expulsion and immunopathology. These findings are supported by worm expulsion upon infection of conditional mutant mice for the IL-10R on IECs. Our findings emphasize the pivotal and complex role of systemic IL-10R signalling on immune cells in promoting microbiota homeostasis and maintaining the intestinal epithelial barrier, thus preventing immunopathology during whipworm infections.
dc.format.mediumElectronic-eCollectionen
dc.languageengen
dc.publisherPublic Library of Science (PLoS)
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectSanger Mouse Genetics Projecten
dc.subject3i consortiumen
dc.subjectIntestinesen
dc.subjectAnimalsen
dc.subjectMice, Inbred C57BLen
dc.subjectMiceen
dc.subjectTrichurisen
dc.subjectTrichuriasisen
dc.subjectDisease Models, Animalen
dc.subjectInterleukinsen
dc.subjectInterleukin-10en
dc.subjectCytokinesen
dc.subjectSignal Transductionen
dc.subjectHomeostasisen
dc.subjectReceptors, Interleukin-10en
dc.subjectGastrointestinal Microbiomeen
dc.titleExclusive dependence of IL-10Rα signalling on intestinal microbiota homeostasis and control of whipworm infection.en
dc.typeArticle
prism.issueIdentifier1en
prism.publicationDate2019en
prism.publicationNamePLoS pathogensen
prism.startingPagee1007265
prism.volume15en
dc.identifier.doi10.17863/CAM.35643
dcterms.dateAccepted2018-12-04en
rioxxterms.versionofrecord10.1371/journal.ppat.1007265en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2019-01-14en
dc.contributor.orcidDuque-Correa, María A [0000-0002-0567-0412]
dc.contributor.orcidJenkins, Timothy [0000-0003-2979-5663]
dc.contributor.orcidMüller, Werner [0000-0002-1297-9725]
dc.contributor.orcidCantacessi, Cinzia [0000-0001-6863-2950]
dc.contributor.orcidDougan, Gordon [0000-0003-0022-965X]
dc.contributor.orcidBerriman, Matthew [0000-0002-9581-0377]
dc.identifier.eissn1553-7374
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idWellcome Trust (100156/Z/12/Z)


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