id,collection,dc.contributor.author,dc.date.accessioned,dc.date.available,dc.date.issued,dc.description.abstract[en],dc.format.extent,dc.identifier.uri,dc.language,dc.rights.uri,dc.subject.ddc,dc.title,dc.type,dcterms.accessRights.openaire,dcterms.bibliographicCitation,dcterms.bibliographicCitation.doi,dcterms.bibliographicCitation.url,refubium.affiliation[de],refubium.mycore.derivateId,refubium.mycore.fudocsId,refubium.note.author,refubium.resourceType.isindependentpub "07126e57-e257-412a-8c97-683a1ce4be9a","fub188/16","Naujoks, Jan||Tabeling, Christoph||Dill, Brian D.||Hoffmann, Christine||Brown, Andrew S.||Kunze, Mareike||Kempa, Stefan||Peter, Andrea||Mollenkopf, Hans-Joachim||Dorhoi, Anca||Kershaw, Olivia||Gruber, Achim D.||Sander, Leif E.||Witzenrath, Martin||Herold, Susanne||Nerlich, Andreas||Hocke, Andreas C.||van Driel, Ian||Suttorp, Norbert||Bedoui, Sammy||Hilbi, Hubert||Trost, Matthias||Opitz, Bastian","2018-06-08T04:08:58Z","2016-07-15T12:23:54.265Z","2016","Macrophages can be niches for bacterial pathogens or antibacterial effector cells depending on the pathogen and signals from the immune system. Here we show that type I and II IFNs are master regulators of gene expression during Legionella pneumophila infection, and activators of an alveolar macrophage- intrinsic immune response that restricts bacterial growth during pneumonia. Quantitative mass spectrometry revealed that both IFNs substantially modify Legionella-containing vacuoles, and comparative analyses reveal distinct subsets of transcriptionally and spatially IFN-regulated proteins. Immune- responsive gene (IRG)1 is induced by IFNs in mitochondria that closely associate with Legionella-containing vacuoles, and mediates production of itaconic acid. This metabolite is bactericidal against intravacuolar L. pneumophila as well as extracellular multidrug-resistant Gram-positive and -negative bacteria. Our study explores the overall role IFNs play in inducing substantial remodeling of bacterial vacuoles and in stimulating production of IRG1-derived itaconic acid which targets intravacuolar pathogens. IRG1 or its product itaconic acid might be therapeutically targetable to fight intracellular and drug-resistant bacteria.","27 Seiten","https://refubium.fu-berlin.de/handle/fub188/16678||http://dx.doi.org/10.17169/refubium-20859","eng","http://creativecommons.org/licenses/by/4.0/","600 Technik, Medizin, angewandte Wissenschaften::630 Landwirtschaft","IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid","Wissenschaftlicher Artikel","open access","PLoS Pathog. - 12 (2016), 2, Artikel Nr. e1005408","10.1371/journal.ppat.1005408","http://dx.doi.org/10.1371/journal.ppat.1005408","Veterinärmedizin","FUDOCS_derivate_000000006781","FUDOCS_document_000000025009","Der Artikel wurde in einer Open-Access-Zeitschrift publiziert.","no"