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dc.contributor.authorPukkila-Worley, Readen_US
dc.contributor.authorFeinbaum, Rhonda L.en_US
dc.contributor.authorMcEwan, Deborah L.en_US
dc.contributor.authorConery, Annie L.en_US
dc.contributor.authorAusubel, Frederick M.en_US
dc.date.accessioned2014-07-07T17:01:27Z
dc.date.issued2014en_US
dc.identifier.citationPukkila-Worley, Read, Rhonda L. Feinbaum, Deborah L. McEwan, Annie L. Conery, and Frederick M. Ausubel. 2014. “The Evolutionarily Conserved Mediator Subunit MDT-15/MED15 Links Protective Innate Immune Responses and Xenobiotic Detoxification.” PLoS Pathogens 10 (5): e1004143. doi:10.1371/journal.ppat.1004143. http://dx.doi.org/10.1371/journal.ppat.1004143.en
dc.identifier.issn1553-7366en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:12406540
dc.description.abstractMetazoans protect themselves from environmental toxins and virulent pathogens through detoxification and immune responses. We previously identified a small molecule xenobiotic toxin that extends survival of Caenorhabditis elegans infected with human bacterial pathogens by activating the conserved p38 MAP kinase PMK-1 host defense pathway. Here we investigate the cellular mechanisms that couple activation of a detoxification response to innate immunity. From an RNAi screen of 1,420 genes expressed in the C. elegans intestine, we identified the conserved Mediator subunit MDT-15/MED15 and 28 other gene inactivations that abrogate the induction of PMK-1-dependent immune effectors by this small molecule. We demonstrate that MDT-15/MED15 is required for the xenobiotic-induced expression of p38 MAP kinase PMK-1-dependent immune genes and protection from Pseudomonas aeruginosa infection. We also show that MDT-15 controls the induction of detoxification genes and functions to protect the host from bacteria-derived phenazine toxins. These data define a central role for MDT-15/MED15 in the coordination of xenobiotic detoxification and innate immune responses.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.ppat.1004143en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4038581/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and Life Sciencesen
dc.subjectImmunologyen
dc.subjectImmune Systemen
dc.subjectInnate Immune Systemen
dc.subjectImmunityen
dc.subjectMicrobiologyen
dc.subjectOrganismsen
dc.subjectAnimalsen
dc.subjectInvertebratesen
dc.subjectNematodaen
dc.subjectCaenorhabditisen
dc.subjectCaenorhabditis Elegansen
dc.subjectMedicine and Health Sciencesen
dc.subjectInfectious Diseasesen
dc.subjectBacterial Diseasesen
dc.subjectPseudomonas Infectionsen
dc.subjectPathology and Laboratory Medicineen
dc.subjectPathogenesisen
dc.subjectHost-Pathogen Interactionsen
dc.subjectModel Organismsen
dc.subjectAnimal Modelsen
dc.titleThe Evolutionarily Conserved Mediator Subunit MDT-15/MED15 Links Protective Innate Immune Responses and Xenobiotic Detoxificationen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS Pathogensen
dash.depositing.authorPukkila-Worley, Readen_US
dc.date.available2014-07-07T17:01:27Z
dc.identifier.doi10.1371/journal.ppat.1004143*
dash.contributor.affiliatedConery, Annie
dash.contributor.affiliatedFeinbaum, Rhonda
dash.contributor.affiliatedAusubel, Frederick
dash.contributor.affiliatedPukkila-Worley, Read


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