Journal article

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

Jan Naujoks, Christoph Tabeling, Brian D Dill, Christine Hoffmann, Andrew S Brown, Mareike Kunze, Stefan Kempa, Andrea Peter, Hans-Joachim Mollenkopf, Anca Dorhoi, Olivia Kershaw, Achim D Gruber, Leif E Sander, Martin Witzenrath, Susanne Herold, Andreas Nerlich, Andreas C Hocke, Ian van Driel, Norbert Suttorp, Sammy Bedoui Show all



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-..

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Awarded by German Research Foundation (DFG)

Awarded by Medical Research Council

Awarded by MRC

Funding Acknowledgements

This work was supported by the International Max Planck Research School for Infectious Diseases and Immunology (IMPRS-IDI; to JN), and the German Research Foundation (DFG; SPP1580/OP86/10-1 to BO, SFB/TR84 to BO, MW, ACH, ADG, LES, and SPP1580/HI1511/3-1 to HH). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.