{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T19:47:44Z","timestamp":1792698464456,"version":"4.5.0"},"reference-count":48,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T00:00:00Z","timestamp":1642032000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Mortality due to sepsis remains unacceptably high, especially for septic shock patients. Murine models have been used to better understand pathophysiology mechanisms. However, the mouse model is still under debate. Herein we investigated the transcriptional response of mice injected with lipopolysaccharide (LPS) and compared it to either human cells stimulated in vitro with LPS or to the blood cells of septic patients. We identified a molecular signature composed of 2331 genes with an FDR median of 0%. This molecular signature is highly enriched in regulated genes in peritoneal macrophages stimulated with LPS. There is significant enrichment in several inflammatory signaling pathways, and in disease terms, such as pneumonia, sepsis, systemic inflammatory response syndrome, severe sepsis, an inflammatory disorder, immune suppression, and septic shock. A significant overlap between the genes upregulated in mouse and human cells stimulated with LPS has been demonstrated. Finally, genes upregulated in mouse cells stimulated with LPS are enriched in genes upregulated in human cells stimulated in vitro and in septic patients, who are at high risk of death. Our results support the hypothesis of common molecular and cellular mechanisms between mouse and human sepsis.<\/jats:p>","DOI":"10.3390\/ijms23020821","type":"journal-article","created":{"date-parts":[[2022,1,13]],"date-time":"2022-01-13T10:57:37Z","timestamp":1642071457000},"page":"821","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Transcriptional Response in a Sepsis Mouse Model Reflects Transcriptional Response in Sepsis Patients"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4363-8093","authenticated-orcid":false,"given":"Florian","family":"Rosier","sequence":"first","affiliation":[{"name":"TAGC, Inserm UMR1090 Aix-Marseille Universit\u00e9, 163 Avenue de Luminy, 13288 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8490-3714","authenticated-orcid":false,"given":"Nicolas Fernandez","family":"Nu\u00f1ez","sequence":"additional","affiliation":[{"name":"TAGC, Inserm UMR1090 Aix-Marseille Universit\u00e9, 163 Avenue de Luminy, 13288 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magali","family":"Torres","sequence":"additional","affiliation":[{"name":"TAGC, Inserm UMR1090 Aix-Marseille Universit\u00e9, 163 Avenue de Luminy, 13288 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B\u00e9atrice","family":"Loriod","sequence":"additional","affiliation":[{"name":"TAGC, Inserm UMR1090 Aix-Marseille Universit\u00e9, 163 Avenue de Luminy, 13288 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9459-3905","authenticated-orcid":false,"given":"Pascal","family":"Rihet","sequence":"additional","affiliation":[{"name":"TAGC, Inserm UMR1090 Aix-Marseille Universit\u00e9, 163 Avenue de Luminy, 13288 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6385-5127","authenticated-orcid":false,"given":"Lydie C.","family":"Pradel","sequence":"additional","affiliation":[{"name":"TAGC, Inserm UMR1090 Aix-Marseille Universit\u00e9, 163 Avenue de Luminy, 13288 Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1001\/jama.2016.0287","article-title":"The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)","volume":"315","author":"Singer","year":"2016","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"108","DOI":"10.3389\/fcell.2019.00108","article-title":"Sepsis: Inflammation Is a Necessary Evil","volume":"7","author":"Nedeva","year":"2019","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1038\/nri3552","article-title":"Sepsis-induced immunosuppression: From cellular dysfunctions to immunotherapy","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Nat. Rev. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e422","DOI":"10.1016\/S1473-3099(19)30567-5","article-title":"Current gaps in sepsis immunology: New opportunities for translational research","volume":"19","author":"Rubio","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1002\/ags3.12194","article-title":"Mechanisms of sepsis-induced immunosuppression and immunological modification therapies for sepsis","volume":"2","author":"Ono","year":"2018","journal-title":"Ann. Gastroenterol. Surg."},{"key":"ref_6","first-page":"426","article-title":"Sepsis-induced immunoparalysis: Mechanisms, markers, and treatment options","volume":"81","author":"Hamers","year":"2015","journal-title":"Minerva Anestesiol"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BST20190029","article-title":"Biomarkers of inflammation and the etiology of sepsis","volume":"48","author":"Grondman","year":"2020","journal-title":"Biochem. Soc. Trans."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Davis, J.S., He, V., Anstey, N.M., and Condon, J.R. (2014). Long term outcomes following hospital admission for sepsis using relative survival analysis: A prospective cohort study of 1092 patients with 5 year follow up. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0112224"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/nri.2017.36","article-title":"The immunopathology of sepsis and potential therapeutic targets","volume":"17","author":"Scicluna","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1089\/sur.2020.047","article-title":"Sepsis and Septic Shock in Low- and Middle-Income Countries","volume":"21","author":"Stephen","year":"2020","journal-title":"Surg. Infect."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e8595","DOI":"10.1590\/1414-431x20198595","article-title":"Sepsis: Evolving concepts and challenges","volume":"52","author":"Salomao","year":"2019","journal-title":"Braz. J. Med. Biol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/S0140-6736(19)32989-7","article-title":"Global, regional, and national sepsis incidence and mortality, 1990\u20132017: Analysis for the Global Burden of Disease Study","volume":"395","author":"Rudd","year":"2020","journal-title":"Lancet"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1093\/ilar\/ilx007","article-title":"Murine Models of Sepsis and Trauma: Can We Bridge the Gap?","volume":"58","author":"Stortz","year":"2017","journal-title":"ILAR J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1134\/S0026893319050108","article-title":"Mouse Models of Sepsis and Septic Shock","volume":"53","author":"Korneev","year":"2019","journal-title":"Mol. Biol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1097\/00024382-200013020-00004","article-title":"Comparison of the mortality and inflammatory response of two models of sepsis: Lipopolysaccharide vs. cecal ligation and puncture","volume":"13","author":"Remick","year":"2000","journal-title":"Shock"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1097\/01.shk.0000191384.34066.85","article-title":"Evaluation of endotoxin models for the study of sepsis","volume":"24","author":"Remick","year":"2005","journal-title":"Shock"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1097\/01.shk.0000191386.18818.0a","article-title":"Rodent models of intra-abdominal infection","volume":"24","author":"Deitch","year":"2005","journal-title":"Shock"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1089\/sur.2012.105","article-title":"Preclinical sepsis models","volume":"13","year":"2012","journal-title":"Surg. Infect."},{"key":"ref_19","first-page":"120","article-title":"Modeling sepsis in the laboratory: Merging sound science with animal well-being","volume":"58","author":"Nemzek","year":"2008","journal-title":"Comp. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"143","DOI":"10.4161\/viru.26083","article-title":"Animal models of sepsis","volume":"5","author":"Fink","year":"2014","journal-title":"Virulence"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1007\/s00011-016-0937-y","article-title":"Sepsis: In search of cure","volume":"65","author":"Lakshmikanth","year":"2016","journal-title":"Inflamm. Res."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1038\/nrd1854","article-title":"Animal models of sepsis: Setting the stage","volume":"4","author":"Buras","year":"2005","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1097\/SHK.0b013e318181a343","article-title":"Experimental models of sepsis and their clinical relevance","volume":"30","author":"Garrido","year":"2008","journal-title":"Shock"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2493","DOI":"10.4049\/jimmunol.168.5.2493","article-title":"Depletion of dendritic cells, but not macrophages, in patients with sepsis","volume":"168","author":"Hotchkiss","year":"2002","journal-title":"J. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e58","DOI":"10.1097\/CCM.0000000000004070","article-title":"Interleukin-17D Aggravates Sepsis by Inhibiting Macrophage Phagocytosis","volume":"48","author":"Yan","year":"2020","journal-title":"Crit. Care Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/S2213-2600(16)00046-1","article-title":"Genomic landscape of the individual host response and outcomes in sepsis: A prospective cohort study","volume":"4","author":"Davenport","year":"2016","journal-title":"Lancet Respir. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1246949","DOI":"10.1126\/science.1246949","article-title":"Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression","volume":"343","author":"Fairfax","year":"2014","journal-title":"Science"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.immuni.2015.12.006","article-title":"Compendium of Immune Signatures Identifies Conserved and Species-Specific Biology in Response to Inflammation","volume":"44","author":"Godec","year":"2016","journal-title":"Immunity"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1097\/CCM.0b013e31819b52fd","article-title":"Gene-expression profiling of peripheral blood mononuclear cells in sepsis","volume":"37","author":"Tang","year":"2009","journal-title":"Crit. Care Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.ebiom.2014.10.003","article-title":"An Endotoxin Tolerance Signature Predicts Sepsis and Organ Dysfunction at Initial Clinical Presentation","volume":"1","author":"Pena","year":"2014","journal-title":"EBioMedicine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"6494","DOI":"10.4049\/jimmunol.0803350","article-title":"Potent phagocytic activity with impaired antigen presentation identifying lipopolysaccharide-tolerant human monocytes: Demonstration in isolated monocytes from cystic fibrosis patients","volume":"182","author":"Jurado","year":"2009","journal-title":"J. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jim.2014.04.007","article-title":"Mouse models for infectious diseases caused by Staphylococcus aureus","volume":"410","author":"Kim","year":"2014","journal-title":"J. Immunol. Methods"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1189\/jlb.0806542","article-title":"The disconnect between animal models of sepsis and human sepsis","volume":"81","author":"Rittirsch","year":"2007","journal-title":"J. Leukoc. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1186\/s13613-019-0543-6","article-title":"Preclinical septic shock research: Why we need an animal ICU","volume":"9","author":"Guillon","year":"2019","journal-title":"Ann. Intensive Care"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1073\/pnas.1222878110","article-title":"Genomic responses in mouse models poorly mimic human inflammatory diseases","volume":"110","author":"Seok","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1073\/pnas.1401965111","article-title":"Genomic responses in mouse models greatly mimic human inflammatory diseases","volume":"112","author":"Takao","year":"2015","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1097\/00003246-199907000-00002","article-title":"Apoptotic cell death in patients with sepsis, shock, and multiple organ dysfunction","volume":"27","author":"Hotchkiss","year":"1999","journal-title":"Crit. Care Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2760","DOI":"10.1101\/gad.1998010","article-title":"Bcl-6 and NF-kappaB cistromes mediate opposing regulation of the innate immune response","volume":"24","author":"Barish","year":"2010","journal-title":"Genes Dev."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4190","DOI":"10.1172\/JCI61716","article-title":"MicroRNA-155 promotes atherosclerosis by repressing Bcl6 in macrophages","volume":"122","author":"Wei","year":"2012","journal-title":"J. Clin. Investig."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1038\/79749","article-title":"BCL-6 regulates chemokine gene transcription in macrophages","volume":"1","author":"Toney","year":"2000","journal-title":"Nat. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"105789","DOI":"10.1016\/j.intimp.2019.105789","article-title":"BCL6 inhibitor FX1 attenuates inflammatory responses in murine sepsis through strengthening BCL6 binding affinity to downstream target gene promoters","volume":"75","author":"Zhang","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e919","DOI":"10.1097\/CCM.0000000000003926","article-title":"Old Mice Demonstrate Organ Dysfunction as well as Prolonged Inflammation, Immunosuppression, and Weight Loss in a Modified Surgical Sepsis Model","volume":"47","author":"Stortz","year":"2019","journal-title":"Crit. Care Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4703","DOI":"10.2741\/3561","article-title":"Sepsis as a model of SIRS","volume":"14","author":"Bhatia","year":"2009","journal-title":"Front. Biosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s42826-020-00079-5","article-title":"Comparison of response to LPS-induced sepsis in three DBA\/2 stocks derived from different sources","volume":"37","author":"Park","year":"2021","journal-title":"Lab. Anim. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1186\/s40635-021-00383-x","article-title":"Sepsis: Deriving biological meaning and clinical applications from high-dimensional data","volume":"9","author":"Schuurman","year":"2021","journal-title":"Intensive Care Med. Exp."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nbt.1630","article-title":"GREAT improves functional interpretation of cis-regulatory regions","volume":"28","author":"McLean","year":"2010","journal-title":"Nat. Biotechnol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/821\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T14:14:52Z","timestamp":1760364892000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/2\/821"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,13]]},"references-count":48,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23020821"],"URL":"https:\/\/doi.org\/10.3390\/ijms23020821","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.12.09.471887","asserted-by":"object"}]},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,1,13]]}}}