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dc.contributor.authorNeubert, Patricken
dc.contributor.authorWeichselbaum, Andreaen
dc.contributor.authorReitinger, Carmenen
dc.contributor.authorSchatz, Valentinen
dc.contributor.authorSchröder, Agnesen
dc.contributor.authorFerdinand, Johnen
dc.contributor.authorSimon, Michaelaen
dc.contributor.authorBär, Anna-Lorenaen
dc.contributor.authorBrochhausen, Christophen
dc.contributor.authorGerlach, Roman Gen
dc.contributor.authorTomiuk, Stefanen
dc.contributor.authorHammer, Karinen
dc.contributor.authorWagner, Stefanen
dc.contributor.authorvan Zandbergen, Geren
dc.contributor.authorBinger, Katrina Jen
dc.contributor.authorMüller, Dominik Nen
dc.contributor.authorKitada, Kentoen
dc.contributor.authorClatworthy, Mennaen
dc.contributor.authorKurts, Christianen
dc.contributor.authorTitze, Jensen
dc.contributor.authorAbdullah, Zeinaben
dc.contributor.authorJantsch, Jonathanen
dc.date.accessioned2019-04-17T23:31:28Z
dc.date.available2019-04-17T23:31:28Z
dc.identifier.issn1554-8627
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/291847
dc.description.abstractInfection and inflammation are able to induce diet-independent Na+-accumulation without commensurate water retention in afflicted tissues, which favors the pro-inflammatory activation of mouse macrophages and augments their antibacterial and antiparasitic activity. While Na+-boosted host defense against the protozoan parasite Leishmania major is mediated by increased expression of the leishmanicidal NOS2 (nitric oxide synthase 2, inducible), the molecular mechanisms underpinning this enhanced antibacterial defense of mouse macrophages with high Na+ (HS) exposure are unknown. Here, we provide evidence that HS-increased antibacterial activity against E. coli was neither dependent on NOS2 nor on the phagocyte oxidase. In contrast, HS-augmented antibacterial defense hinged on HIF1A (hypoxia inducible factor 1, alpha subunit)-dependent increased autophagy, and NFAT5 (nuclear factor of activated T cells 5)-dependent targeting of intracellular E. coli to acidic autolysosomal compartments. Overall, these findings suggest that the autolysosomal compartment is a novel target of Na+- modulated cell autonomous innate immunity.
dc.description.sponsorshipThis work was supported by the Deutsche Forschungsgemeinschaft [WA 2539/4-1, 5-1, 7-1]; Deutsche Forschungsgemeinschaft (DE) [JA 1993/ 4-1]; Universitätsklinikum Regensburg [Reform C]; NIHR Cambridge Blood and Transplant Research Unit Organ Donation.
dc.languageenen
dc.publisherTaylor & Francis
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0/
dc.titleHIF1A and NFAT5 coordinate Na+-boosted antibacterial defense via enhanced autophagy and autolysosomal targetingen
dc.typeArticle
prism.publicationNameAutophagyen
dc.identifier.doi10.17863/CAM.39007
dcterms.dateAccepted2019-02-22en
rioxxterms.versionofrecord10.1080/15548627.2019.1596483en
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
rioxxterms.licenseref.startdate2019-02-22en
dc.contributor.orcidFerdinand, John [0000-0003-0936-0128]
dc.contributor.orcidClatworthy, Menna [0000-0002-3340-9828]
dc.identifier.eissn1554-8635
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NIHR BTRU-2014-10027)
cam.issuedOnline2019-04-14en


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