Publikationsdatenbank
IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid (2016)
- Art
- Zeitschriftenartikel / wissenschaftlicher Beitrag
- Autoren
- 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 (WE 12)
- Gruber, Achim D (WE 12)
- 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
- Quelle
- PLoS Pathogens; 12(2) — S. 1–27
- ISSN: 1553-7366
- Sprache
- Englisch
- Verweise
- URL (Volltext): http://journals.plos.org/plospathogens/article/asset?id=10.1371%2Fjournal.ppat.1005408.PDF
- DOI: 10.1371/journal.ppat.1005408
- Pubmed: 26829557
- Kontakt
- Institut für Tierpathologie
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Robert-von-Ostertag-Str. 15
Gebäude 12
14163 Berlin
+49 30 838 62450 - Abstract / Zusammenfassung
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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.