Show simple item record

dc.contributor.authorBerger, CNen_US
dc.contributor.authorCrepin, VFen_US
dc.contributor.authorRoumeliotis, TIen_US
dc.contributor.authorWright, JCen_US
dc.contributor.authorSerafini, Nen_US
dc.contributor.authorPevsner-Fischer, Men_US
dc.contributor.authorYu, Len_US
dc.contributor.authorElinav, Een_US
dc.contributor.authorDi Santo, JPen_US
dc.contributor.authorChoudhary, JSen_US
dc.contributor.authorFrankel, Gen_US
dc.coverage.spatialUnited Statesen_US
dc.date.accessioned2019-02-20T07:41:22Z
dc.date.issued2018-10en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30365535en_US
dc.identifierPPATHOGENS-D-18-01314en_US
dc.identifier.citationPLoS Pathog, 2018, 14 (10), pp. e1007406 - ?en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3057
dc.identifier.eissn1553-7374en_US
dc.identifier.doi10.1371/journal.ppat.1007406en_US
dc.description.abstractInfection with Citrobacter rodentium triggers robust tissue damage repair responses, manifested by secretion of IL-22, in the absence of which mice succumbed to the infection. Of the main hallmarks of C. rodentium infection are colonic crypt hyperplasia (CCH) and dysbiosis. In order to colonize the host and compete with the gut microbiota, C. rodentium employs a type III secretion system (T3SS) that injects effectors into colonic intestinal epithelial cells (IECs). Once injected, the effectors subvert processes involved in innate immune responses, cellular metabolism and oxygenation of the mucosa. Importantly, the identity of the effector/s triggering the tissue repair response is/are unknown. Here we report that the effector EspO ,an orthologue of OspE found in Shigella spp, affects proliferation of IECs 8 and 14 days post C. rodentium infection as well as secretion of IL-22 from colonic explants. While we observed no differences in the recruitment of group 3 innate lymphoid cells (ILC3s) and T cells, which are the main sources of IL-22 at the early and late stages of C. rodentium infection respectively, infection with ΔespO was characterized by diminished recruitment of sub-mucosal neutrophils, which coincided with lower abundance of Mmp9 and chemokines (e.g. S100a8/9) in IECs. Moreover, mice infected with ΔespO triggered significantly lesser nutritional immunity (e.g. calprotectin, Lcn2) and expression of antimicrobial peptides (Reg3β, Reg3γ) compared to mice infected with WT C. rodentium. This overlapped with a decrease in STAT3 phosphorylation in IECs. Importantly, while the reduced CCH and abundance of antimicrobial proteins during ΔespO infection did not affect C. rodentium colonization or the composition of commensal Proteobacteria, they had a subtle consequence on Firmicutes subpopulations. EspO is the first bacterial virulence factor that affects neutrophil recruitment and secretion of IL-22, as well as expression of antimicrobial and nutritional immunity proteins in IECs.en_US
dc.format.extente1007406 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.subjectAnimalsen_US
dc.subjectAntimicrobial Cationic Peptidesen_US
dc.subjectCitrobacter rodentiumen_US
dc.subjectEnterobacteriaceae Infectionsen_US
dc.subjectFemaleen_US
dc.subjectImmunity, Innateen_US
dc.subjectIntestinal Mucosaen_US
dc.subjectMiceen_US
dc.subjectMice, Inbred C57BLen_US
dc.subjectType III Secretion Systemsen_US
dc.titleThe Citrobacter rodentium type III secretion system effector EspO affects mucosal damage repair and antimicrobial responses.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-10-15en_US
rioxxterms.versionofrecord10.1371/journal.ppat.1007406en_US
rioxxterms.licenseref.startdate2018-10en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfPLoS Pathogen_US
pubs.issue10en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.publication-statusPublished onlineen_US
pubs.volume14en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorChoudhary, Jyotien_US
dc.contributor.icrauthorWright, Jamesen_US
dc.contributor.icrauthorRoumeliotis, Theodorosen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/