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dc.contributor.authorNaujoks, J
dc.contributor.authorTabeling, C
dc.contributor.authorDill, BD
dc.contributor.authorHoffmann, C
dc.contributor.authorBrown, AS
dc.contributor.authorKunze, M
dc.contributor.authorKempa, S
dc.contributor.authorPeter, A
dc.contributor.authorMollenkopf, H-J
dc.contributor.authorDorhoi, A
dc.contributor.authorKershaw, O
dc.contributor.authorGruber, AD
dc.contributor.authorSander, LE
dc.contributor.authorWitzenrath, M
dc.contributor.authorHerold, S
dc.contributor.authorNerlich, A
dc.contributor.authorHocke, AC
dc.contributor.authorvan Driel, I
dc.contributor.authorSuttorp, N
dc.contributor.authorBedoui, S
dc.contributor.authorHilbi, H
dc.contributor.authorTrost, M
dc.contributor.authorOpitz, B
dc.date.accessioned2021-02-03T23:40:10Z
dc.date.available2021-02-03T23:40:10Z
dc.date.issued2016-02-01
dc.identifierpii: PPATHOGENS-D-15-01903
dc.identifier.citationNaujoks, J., Tabeling, C., Dill, B. D., Hoffmann, C., Brown, A. S., Kunze, M., Kempa, S., Peter, A., Mollenkopf, H. -J., Dorhoi, A., Kershaw, O., Gruber, A. D., Sander, L. E., Witzenrath, M., Herold, S., Nerlich, A., Hocke, A. C., van Driel, I., Suttorp, N. ,... Opitz, B. (2016). IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid. PLOS PATHOGENS, 12 (2), https://doi.org/10.1371/journal.ppat.1005408.
dc.identifier.issn1553-7366
dc.identifier.urihttp://hdl.handle.net/11343/258941
dc.description.abstractMacrophages 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.
dc.languageEnglish
dc.publisherPUBLIC LIBRARY SCIENCE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleIFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid
dc.typeJournal Article
dc.identifier.doi10.1371/journal.ppat.1005408
melbourne.affiliation.departmentMicrobiology and Immunology
melbourne.affiliation.departmentSchool of Biomedical Sciences
melbourne.affiliation.departmentBiochemistry and Molecular Biology
melbourne.affiliation.facultyMedicine, Dentistry & Health Sciences
melbourne.source.titlePLoS Pathogens
melbourne.source.volume12
melbourne.source.issue2
dc.rights.licenseCC BY
melbourne.elementsid1043574
melbourne.contributor.authorBedoui, Sammy
melbourne.contributor.authorBROWN, ANDREW
melbourne.contributor.authorvan Driel, Ian
dc.identifier.eissn1553-7374
melbourne.accessrightsOpen Access


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