Listeria monocytogenes infection rewires host metabolism with regulatory input from type I interferons

Autor(en)

Duygu Demiroz, Ekaterini Platanitis, Michael Bryant, Philipp Fischer, Michaela Prchal-Murphy, Alexander Lercher, Caroline Lassnig, Manuela Baccarini, Mathias Müller, Andreas Bergthaler, Veronika Sexl, Marlies Dolezal, Thomas Decker

Abstrakt

Listeria monocytogenes (L. monocytogenes) is a food-borne bacterial pathogen. Innate immunity to L. monocytogenes is profoundly affected by type I interferons (IFN-I). Here we investigated host metabolism in L. monocytogenes-infected mice and its potential control by IFN-I. Accordingly, we used animals lacking either the IFN-I receptor (IFNAR) or IRF9, a subunit of ISGF3, the master regulator of IFN-I-induced genes. Transcriptomes and metabolite profiles showed that L. monocytogenes infection induces metabolic rewiring of the liver. This affects various metabolic pathways including fatty acid (FA) metabolism and oxidative phosphorylation and is partially dependent on IFN-I signaling. Livers and macrophages from Ifnar1-/- mice employ increased glutaminolysis in an IRF9-independent manner, possibly to readjust TCA metabolite levels due to reduced FA oxidation. Moreover, FA oxidation inhibition provides protection from L. monocytogenes infection, explaining part of the protection of Irf9-/- and Ifnar1-/- mice. Our findings define a role of IFN-I in metabolic regulation during L. monocytogenes infection. Metabolic differences between Irf9-/- and Ifnar1-/- mice may underlie the different susceptibility of these mice against lethal infection with L. monocytogenes.

Organisation(en)

Department für Mikrobiologie, Immunbiologie und Genetik

Externe Organisation(en)

Veterinärmedizinische Universität Wien, Österreichische Akademie der Wissenschaften (ÖAW), The Rockefeller University, Medizinische Universität Wien, Universität Wien

Journal

PLoS Pathogens

Band

17

Anzahl der Seiten

23

ISSN

1553-7366

DOI

https://doi.org/10.1371/journal.ppat.1009697

Publikationsdatum

07-2021

Peer-reviewed

Ja

ÖFOS 2012

403016 Immunologie (Veterinärmedizin), 106022 Mikrobiologie

Schlagwörter

ASJC Scopus Sachgebiete

Genetics, Molecular Biology, Virology, Parasitology, Microbiology, Immunology

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/139cda34-4c9f-4932-8eaf-cc5eaad7470a