Details

Autor(en) / Beteiligte

• 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
• Zamboni, Dario S.

Titel

IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid

Ist Teil von

• PLoS pathogens, 2016-02, Vol.12 (2), p.e1005408-e1005408

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2016

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.