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.; Driel, Ian van; Suttorp, Norbert; Bedoui, Sammy; Hilbi, Hubert; Trost, Matthias; Opitz, Bastian
(2016):
IFNs Modify the Proteome of Legionella-Containing Vacuoles and Restrict Infection Via IRG1-Derived Itaconic Acid.
In: PLOS Pathogens 12(2), e1005408 |
| 8MB |
Abstract
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.
Item Type: | Journal article |
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Faculties: | Medicine > Adolf Butenandt Institute |
Subjects: | 600 Technology > 610 Medicine and health |
URN: | urn:nbn:de:bvb:19-epub-38092-1 |
ISSN: | 1553-7366 |
Language: | English |
ID Code: | 38092 |
Deposited On: | 04. May 2017 13:11 |
Last Modified: | 04. Nov 2020 14:45 |
- BASE
- 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.
- Driel, Ian van
- Suttorp, Norbert
- Bedoui, Sammy
- Hilbi, Hubert
- Trost, Matthias
- Opitz, Bastian
- Google Scholar
- 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.
- Driel, Ian van
- Suttorp, Norbert
- Bedoui, Sammy
- Hilbi, Hubert
- Trost, Matthias
- Opitz, Bastian