dc.contributor.author | Berger, CN | |
dc.contributor.author | Crepin, VF | |
dc.contributor.author | Roumeliotis, TI | |
dc.contributor.author | Wright, JC | |
dc.contributor.author | Serafini, N | |
dc.contributor.author | Pevsner-Fischer, M | |
dc.contributor.author | Yu, L | |
dc.contributor.author | Elinav, E | |
dc.contributor.author | Di Santo, JP | |
dc.contributor.author | Choudhary, JS | |
dc.contributor.author | Frankel, G | |
dc.date.accessioned | 2019-02-20T07:41:22Z | |
dc.date.issued | 2018-10-01 | |
dc.identifier.citation | PLoS pathogens, 2018, 14 (10), pp. e1007406 - ? | |
dc.identifier.issn | 1553-7366 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3057 | |
dc.identifier.eissn | 1553-7374 | |
dc.identifier.doi | 10.1371/journal.ppat.1007406 | |
dc.description.abstract | Infection 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. | |
dc.format | Electronic-eCollection | |
dc.format.extent | e1007406 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | PUBLIC LIBRARY SCIENCE | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Intestinal Mucosa | |
dc.subject | Animals | |
dc.subject | Mice, Inbred C57BL | |
dc.subject | Mice | |
dc.subject | Citrobacter rodentium | |
dc.subject | Enterobacteriaceae Infections | |
dc.subject | Antimicrobial Cationic Peptides | |
dc.subject | Female | |
dc.subject | Immunity, Innate | |
dc.subject | Type III Secretion Systems | |
dc.title | The Citrobacter rodentium type III secretion system effector EspO affects mucosal damage repair and antimicrobial responses. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-10-15 | |
rioxxterms.versionofrecord | 10.1371/journal.ppat.1007406 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-10-26 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | PLoS pathogens | |
pubs.issue | 10 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Functional Proteomics Group | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Functional Proteomics Group | |
pubs.publication-status | Published | |
pubs.volume | 14 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Functional Proteomics Group | |
dc.contributor.icrauthor | Roumeliotis, Theodoros | |
dc.contributor.icrauthor | Wright, James | |
dc.contributor.icrauthor | Choudhary, Jyoti | |