{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T09:03:20Z","timestamp":1790327000389,"version":"4.1.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T00:00:00Z","timestamp":1625702400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P25186-B22, SFB F6101"],"award-info":[{"award-number":["P25186-B22, SFB F6101"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P25186-B22, SFB F6101"],"award-info":[{"award-number":["P25186-B22, SFB F6101"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["P25186-B22, SFB F6101"],"award-info":[{"award-number":["P25186-B22, SFB F6101"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["SFB F6103"],"award-info":[{"award-number":["SFB F6103"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]},{"name":"UniDoc Fellowship, University of Vienna"},{"DOI":"10.13039\/501100001822","name":"\u00d6sterreichischen Akademie der Wissenschaften","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001822","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["677006"],"award-info":[{"award-number":["677006"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Listeria monocytogenes<\/jats:italic>(<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>) is a food-borne bacterial pathogen. Innate immunity to<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>is profoundly affected by type I interferons (IFN-I). Here we investigated host metabolism in<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes-<\/jats:italic>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<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>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<jats:italic>Ifnar1<\/jats:italic><jats:sup>-\/-<\/jats:sup>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<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>infection, explaining part of the protection of<jats:italic>Irf9<\/jats:italic><jats:sup>-\/-<\/jats:sup>and<jats:italic>Ifnar1<\/jats:italic><jats:sup>-\/-<\/jats:sup>mice. Our findings define a role of IFN-I in metabolic regulation during<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>infection. Metabolic differences between<jats:italic>Irf9<\/jats:italic><jats:sup>-\/-<\/jats:sup>and<jats:italic>Ifnar1<\/jats:italic><jats:sup>-\/-<\/jats:sup>mice may underlie the different susceptibility of these mice against lethal infection with<jats:italic>L<\/jats:italic>.<jats:italic>monocytogenes<\/jats:italic>.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009697","type":"journal-article","created":{"date-parts":[[2021,7,8]],"date-time":"2021-07-08T17:30:29Z","timestamp":1625765429000},"page":"e1009697","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":20,"title":["Listeria monocytogenes infection rewires host metabolism with regulatory input from type I interferons"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6854-7852","authenticated-orcid":true,"given":"Duygu","family":"Demiroz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3371-2819","authenticated-orcid":true,"given":"Ekaterini","family":"Platanitis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1333-4328","authenticated-orcid":true,"given":"Michael","family":"Bryant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Fischer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Prchal-Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3478-5304","authenticated-orcid":true,"given":"Alexander","family":"Lercher","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7905-3620","authenticated-orcid":true,"given":"Caroline","family":"Lassnig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3033-391X","authenticated-orcid":true,"given":"Manuela","family":"Baccarini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7879-3552","authenticated-orcid":true,"given":"Mathias","family":"M\u00fcller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Bergthaler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Sexl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies","family":"Dolezal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9683-0620","authenticated-orcid":true,"given":"Thomas","family":"Decker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,7,8]]},"reference":[{"key":"ppat.1009697.ref001","first-page":"255","article-title":"WHO estimates of the global burden of foodborne diseases: foodborne disease burden epidemiology reference group 2007\u20132015","author":"WHO","year":"2015","journal-title":"WHO estimates of the global burden of foodborne diseases: foodborne disease burden epidemiology reference group 2007\u20132015"},{"key":"ppat.1009697.ref002","first-page":"24","article-title":"Metabolic host responses to infection by intracellular bacterial pathogens","volume":"3","author":"W Eisenreich","year":"2013","journal-title":"Front Cell Infect Mi"},{"key":"ppat.1009697.ref003","doi-asserted-by":"crossref","first-page":"e50679","DOI":"10.1371\/journal.pone.0050679","article-title":"Listeria monocytogenes Infection Causes Metabolic Shifts in Drosophila melanogaster","volume":"7","author":"MC Chambers","year":"2012","journal-title":"Plos One"},{"key":"ppat.1009697.ref004","doi-asserted-by":"crossref","first-page":"e1000150","DOI":"10.1371\/journal.pbio.1000150","article-title":"The Role of Anorexia in Resistance and Tolerance to Infections in Drosophila","volume":"7","author":"JS Ayres","year":"2009","journal-title":"Plos Biol"},{"key":"ppat.1009697.ref005","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1016\/j.cell.2016.07.026","article-title":"Opposing Effects of Fasting Metabolism on Tissue Tolerance in Bacterial and Viral Inflammation","volume":"166","author":"A Wang","year":"2016","journal-title":"Cell"},{"key":"ppat.1009697.ref006","doi-asserted-by":"crossref","first-page":"e0180900","DOI":"10.1371\/journal.pone.0180900","article-title":"Fasting metabolism modulates the interleukin-12\/interleukin-10 cytokine axis","volume":"12","author":"JJ Kovarik","year":"2017","journal-title":"Plos One"},{"key":"ppat.1009697.ref007","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/S0031-9384(98)00199-1","article-title":"2-Deoxy-D-Glucose\u2013Induced Metabolic Stress Enhances Resistance to Listeria monocytogenes Infection in Mice","volume":"65","author":"E Miller","year":"1998","journal-title":"Physiol Behav"},{"key":"ppat.1009697.ref008","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1038\/nri1684","article-title":"The Yin and Yang of type I interferon activity in bacterial infection","volume":"5","author":"T Decker","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"ppat.1009697.ref009","first-page":"50","article-title":"The bacterial pathogen Listeria monocytogenes and the interferon family: type I, type II and type III interferons","volume":"4","author":"O Dussurget","year":"2014","journal-title":"Front Cell Infect Mi"},{"key":"ppat.1009697.ref010","doi-asserted-by":"crossref","first-page":"29","DOI":"10.3389\/fimmu.2017.00029","article-title":"Canonical and Non-Canonical Aspects of JAK\u2013STAT Signaling: Lessons from Interferons for Cytokine Responses","volume":"8","author":"A Majoros","year":"2017","journal-title":"Front Immunol"},{"key":"ppat.1009697.ref011","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1038\/nri.2016.70","article-title":"A guide to immunometabolism for immunologists","volume":"16","author":"LAJ O\u2019Neill","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"ppat.1009697.ref012","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1016\/j.immuni.2016.06.006","article-title":"Type 1 Interferons Induce Changes in Core Metabolism that Are Critical for Immune Function","volume":"44","author":"D Wu","year":"2016","journal-title":"Immunity"},{"key":"ppat.1009697.ref013","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1002\/hep.26368","article-title":"Interferon regulatory factor 9 protects against hepatic insulin resistance and steatosis in male mice","volume":"58","author":"X Wang","year":"2013","journal-title":"Hepatology"},{"key":"ppat.1009697.ref014","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1128\/iai.5.6.863-871.1972","article-title":"Mechanisms of Pathogenesis in Listeria monocytogenes Infection V. Early Imbalance in Host Energy Metabolism During Experimental Listeriosis","volume":"5","author":"RE McCallum","year":"1972","journal-title":"Infection and Immunity"},{"key":"ppat.1009697.ref015","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1128\/iai.5.6.872-878.1972","article-title":"Mechanisms of Pathogenesis in Listeria monocytogenesInfection VI. Oxidative Phosphorylation in Mouse Liver Mitochondria During Experimental Listeriosis","volume":"5","author":"RE McCallum","year":"1972","journal-title":"Infection and Immunity"},{"key":"ppat.1009697.ref016","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1084\/jem.20040712","article-title":"Type I Interferon Production Enhances Susceptibility to Listeria monocytogenes Infection","volume":"200","author":"RM O\u2019Connell","year":"2004","journal-title":"J Exp Medicine"},{"key":"ppat.1009697.ref017","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1084\/jem.20040976","article-title":"Mice Lacking the Type I Interferon Receptor Are Resistant to Listeria monocytogenes","volume":"200","author":"V Auerbuch","year":"2004","journal-title":"J Exp Medicine"},{"key":"ppat.1009697.ref018","doi-asserted-by":"crossref","first-page":"e65007","DOI":"10.1371\/journal.pone.0065007","article-title":"Route of Infection Determines the Impact of Type I Interferons on Innate Immunity to Listeria monocytogenes","volume":"8","author":"E Kernbauer","year":"2013","journal-title":"Plos One"},{"key":"ppat.1009697.ref019","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.it.2014.10.006","article-title":"Intersection of mTOR and STAT signaling in immunity","volume":"36","author":"D Saleiro","year":"2015","journal-title":"Trends Immunol"},{"key":"ppat.1009697.ref020","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.it.2006.09.005","article-title":"Lymphocyte apoptosis as an immune subversion strategy of microbial pathogens","volume":"27","author":"JA Carrero","year":"2006","journal-title":"Trends Immunol"},{"key":"ppat.1009697.ref021","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1146\/annurev.immunol.26.021607.090326","article-title":"Monocyte-Mediated Defense Against Microbial Pathogens","volume":"26","author":"NV Serbina","year":"2008","journal-title":"Immunology"},{"key":"ppat.1009697.ref022","first-page":"679","article-title":"Listeria monocytogenes induces apoptosis of infected hepatocytes","volume":"156","author":"HW Rogers","year":"1996","journal-title":"J Immunol Baltim Md 1950"},{"key":"ppat.1009697.ref023","doi-asserted-by":"crossref","first-page":"8","DOI":"10.3390\/pathogens7010008","article-title":"Listeria monocytogenes: The Impact of Cell Death on Infection and Immunity","volume":"7","author":"CE McDougal","year":"2018","journal-title":"Pathogens"},{"key":"ppat.1009697.ref024","first-page":"851","article-title":"Listeria monocytogenes: cell biology of invasion and intracellular growth","volume":"6","author":"J Pizarro-Cerd\u00e1","year":"2019","journal-title":"Microbiol Spectr"},{"key":"ppat.1009697.ref025","doi-asserted-by":"crossref","first-page":"630","DOI":"10.3389\/fimmu.2016.00630","article-title":"Effects of Interferons and Viruses on Metabolism","volume":"7","author":"SD Fritsch","year":"2016","journal-title":"Front Immunol"},{"key":"ppat.1009697.ref026","doi-asserted-by":"crossref","first-page":"2921","DOI":"10.1038\/s41467-019-10970-y","article-title":"A molecular switch from STAT2-IRF9 to ISGF3 underlies interferon-induced gene transcription","volume":"10","author":"E Platanitis","year":"2019","journal-title":"Nat Commun"},{"key":"ppat.1009697.ref027","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1042\/BST0340223","article-title":"Regulation of acetyl-CoA carboxylase","volume":"34","author":"RW Brownsey","year":"2006","journal-title":"Biochem Soc T"},{"key":"ppat.1009697.ref028","doi-asserted-by":"crossref","first-page":"e1008973","DOI":"10.1371\/journal.ppat.1008973","article-title":"Hepatocyte-intrinsic type I interferon signaling reprograms metabolism and reveals a novel compensatory mechanism of the tryptophan-kynurenine pathway in viral hepatitis","volume":"16","author":"A Lercher","year":"2020","journal-title":"Plos Pathog"},{"key":"ppat.1009697.ref029","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/j.immuni.2019.10.014","article-title":"Type I Interferon Signaling Disrupts the Hepatic Urea Cycle and Alters Systemic Metabolism to Suppress T Cell Function","volume":"51","author":"A Lercher","year":"2019","journal-title":"Immunity"},{"key":"ppat.1009697.ref030","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/j.celrep.2019.05.105","article-title":"Microbiota-Driven Tonic Interferon Signals in Lung Stromal Cells Protect from Influenza Virus Infection","volume":"28","author":"KC Bradley","year":"2019","journal-title":"Cell Reports"},{"key":"ppat.1009697.ref031","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/nature11986","article-title":"Succinate is an inflammatory signal that induces IL-1\u03b2 through HIF-1\u03b1","volume":"496","author":"GM Tannahill","year":"2013","journal-title":"Nature"},{"key":"ppat.1009697.ref032","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/nri1604","article-title":"Mechanisms of type-I- and type-II-interferon-mediated signalling","volume":"5","author":"LC Platanias","year":"2005","journal-title":"Nat Rev Immunol"},{"key":"ppat.1009697.ref033","doi-asserted-by":"crossref","first-page":"e1000598","DOI":"10.1371\/journal.pbio.1000598","article-title":"Host Defense against Viral Infection Involves Interferon Mediated Down-Regulation of Sterol Biosynthesis","volume":"9","author":"M Blanc","year":"2011","journal-title":"Plos Biol"},{"key":"ppat.1009697.ref034","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1016\/j.cell.2015.11.045","article-title":"Limiting Cholesterol Biosynthetic Flux Spontaneously Engages Type I IFN Signaling","volume":"163","author":"AG York","year":"2015","journal-title":"Cell"},{"key":"ppat.1009697.ref035","doi-asserted-by":"crossref","first-page":"e1004021","DOI":"10.1371\/journal.ppat.1004021","article-title":"De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection","volume":"10","author":"MD Greseth","year":"2014","journal-title":"Plos Pathog"},{"key":"ppat.1009697.ref036","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.jss.2018.11.047","article-title":"GABA, \u03b3-Aminobutyric Acid, Protects Against Severe Liver Injury","volume":"236","author":"T Hata","year":"2019","journal-title":"J Surg Res"},{"key":"ppat.1009697.ref037","doi-asserted-by":"crossref","first-page":"4184","DOI":"10.1038\/s41467-018-06487-5","article-title":"GABAergic signaling linked to autophagy enhances host protection against intracellular bacterial infections","volume":"9","author":"JK Kim","year":"2018","journal-title":"Nat Commun"},{"key":"ppat.1009697.ref038","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1161\/HYPERTENSIONAHA.113.02083","article-title":"Interferon Regulatory Factor 9 Protects Against Cardiac Hypertrophy by Targeting Myocardin","volume":"63","author":"D-S Jiang","year":"2014","journal-title":"Hypertension"},{"key":"ppat.1009697.ref039","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.jhep.2014.08.022","article-title":"Interferon regulatory factor 9 is a key mediator of hepatic ischemia\/reperfusion injury","volume":"62","author":"P-X Wang","year":"2015","journal-title":"J Hepatol"},{"key":"ppat.1009697.ref040","volume-title":"R: A language and environment for statistical computing","author":"R_Core_Team","year":"2019"},{"key":"ppat.1009697.ref041","article-title":"emmeans: Estimated Marginal Means, aka Least-Squares Means","author":"R Lenth","year":"2020","journal-title":"emmeans: Estimated Marginal Means, aka Least-Squares Means"},{"key":"ppat.1009697.ref042","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","year":"1995","journal-title":"Journal of the Royal Statistical Society"},{"key":"ppat.1009697.ref043","article-title":"factoextra: Extract and Visualize the Results of Multivariate Data Analyses","author":"A Kassambara","year":"2020","journal-title":"factoextra: Extract and Visualize the Results of Multivariate Data Analyses"}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009697","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T18:49:39Z","timestamp":1725389379000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1009697"}},"subtitle":[],"editor":[{"given":"Mary","family":"O\u2019Riordan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,7,8]]},"references-count":43,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2021,7,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1009697","relation":{},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,8]]}}}