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dc.contributor.authorBlohmke, CJen_US
dc.contributor.authorDarton, TCen_US
dc.contributor.authorJones, Cen_US
dc.contributor.authorSuarez, NMen_US
dc.contributor.authorWaddington, CSen_US
dc.contributor.authorAngus, Ben_US
dc.contributor.authorZhou, Len_US
dc.contributor.authorHill, Jen_US
dc.contributor.authorClare, Sen_US
dc.contributor.authorKane, Len_US
dc.contributor.authorMukhopadhyay, Sen_US
dc.contributor.authorSchreiber, Fen_US
dc.contributor.authorDuque-Correa, MAen_US
dc.contributor.authorWright, JCen_US
dc.contributor.authorRoumeliotis, TIen_US
dc.contributor.authorYu, Len_US
dc.contributor.authorChoudhary, JSen_US
dc.contributor.authorMejias, Aen_US
dc.contributor.authorRamilo, Oen_US
dc.contributor.authorShanyinde, Men_US
dc.contributor.authorSztein, MBen_US
dc.contributor.authorKingsley, RAen_US
dc.contributor.authorLockhart, Sen_US
dc.contributor.authorLevine, MMen_US
dc.contributor.authorLynn, DJen_US
dc.contributor.authorDougan, Gen_US
dc.contributor.authorPollard, AJen_US
dc.date.accessioned2020-10-16T09:38:49Z
dc.date.issued2016-05-23en_US
dc.identifier.citationThe Journal of experimental medicine, 2016, 213 (6), pp. 1061 - 1077en_US
dc.identifier.issn0022-1007en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4174
dc.identifier.eissn1540-9538en_US
dc.identifier.doi10.1084/jem.20151025en_US
dc.description.abstractEnteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. Typhi, we detected significant cytokine responses within 12 h of bacterial ingestion. These early responses did not correlate with subsequent clinical disease outcomes and likely indicate initial host-pathogen interactions in the gut mucosa. In participants developing enteric fever after oral infection, marked transcriptional and cytokine responses during acute disease reflected dominant type I/II interferon signatures, which were significantly associated with bacteremia. Using a murine and macrophage infection model, we validated the pivotal role of this response in the expression of proteins of the host tryptophan metabolism during Salmonella infection. Corresponding alterations in tryptophan catabolites with immunomodulatory properties in serum of participants with typhoid fever confirmed the activity of this pathway, and implicate a central role of host tryptophan metabolism in the pathogenesis of typhoid fever.en_US
dc.formatPrint-Electronicen_US
dc.format.extent1061 - 1077en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc-sa/4.0en_US
dc.subjectHumansen_US
dc.subjectSalmonella typhien_US
dc.subjectTyphoid Feveren_US
dc.subjectTryptophanen_US
dc.subjectInterferon Type Ien_US
dc.subjectAdulten_US
dc.subjectMiddle Ageden_US
dc.subjectFemaleen_US
dc.subjectMaleen_US
dc.subjectInterferon-gammaen_US
dc.subjectImmunomodulationen_US
dc.titleInterferon-driven alterations of the host's amino acid metabolism in the pathogenesis of typhoid fever.en_US
dc.typeJournal Article
dcterms.dateAccepted2016-04-08en_US
rioxxterms.versionofrecord10.1084/jem.20151025en_US
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-sa/4.0en_US
rioxxterms.licenseref.startdate2016-05-23en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfThe Journal of experimental medicineen_US
pubs.issue6en_US
pubs.notesNot knownen_US
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-statusPublisheden_US
pubs.volume213en_US
pubs.embargo.termsNot knownen_US
icr.researchteamFunctional Proteomics Groupen_US
dc.contributor.icrauthorWright, Jamesen_US
dc.contributor.icrauthorChoudhary, Jyotien_US


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