In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 7 ( 2021-7-8), p. e1009697-
Abstract:
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 .
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009697
DOI:
10.1371/journal.ppat.1009697.g001
DOI:
10.1371/journal.ppat.1009697.g002
DOI:
10.1371/journal.ppat.1009697.g003
DOI:
10.1371/journal.ppat.1009697.g004
DOI:
10.1371/journal.ppat.1009697.g005
DOI:
10.1371/journal.ppat.1009697.g006
DOI:
10.1371/journal.ppat.1009697.s001
DOI:
10.1371/journal.ppat.1009697.s002
DOI:
10.1371/journal.ppat.1009697.s003
DOI:
10.1371/journal.ppat.1009697.s004
DOI:
10.1371/journal.ppat.1009697.s005
DOI:
10.1371/journal.ppat.1009697.s006
DOI:
10.1371/journal.ppat.1009697.s007
DOI:
10.1371/journal.ppat.1009697.s008
DOI:
10.1371/journal.ppat.1009697.s009
DOI:
10.1371/journal.ppat.1009697.s010
DOI:
10.1371/journal.ppat.1009697.s011
DOI:
10.1371/journal.ppat.1009697.s012
DOI:
10.1371/journal.ppat.1009697.s013
DOI:
10.1371/journal.ppat.1009697.s014
DOI:
10.1371/journal.ppat.1009697.r001
DOI:
10.1371/journal.ppat.1009697.r002
DOI:
10.1371/journal.ppat.1009697.r003
DOI:
10.1371/journal.ppat.1009697.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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