{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T07:05:22Z","timestamp":1787641522149,"version":"build-2736575974"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T00:00:00Z","timestamp":1631232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in \u201comics\u201d technologies have provided valuable tools to unravel the mechanisms involved in the pathogenesis of this disease. In this study, we performed shotgun mass spectrometry in peripheral blood mononuclear cells (PBMC) from septic patients (N=24) and healthy controls (N=9) and combined these results with two public microarray leukocytes datasets. Through combination of transcriptome and proteome profiling, we identified 170 co\u2010differentially expressed genes\/proteins. Among these, 122 genes\/proteins displayed the same expression trend. Ingenuity Pathway Analysis revealed pathways related to lymphocyte functions with decreased status, and defense processes that were predicted to be strongly increased. Protein-protein interaction network analyses revealed two densely connected regions, which mainly included down\u2010regulated genes\/proteins that were related to the transcription of RNA, translation of proteins, and mitochondrial translation. Additionally, we identified one module comprising of up\u2010regulated genes\/proteins, which were mainly related to low-density neutrophils (LDNs). LDNs were reported in sepsis and in COVID-19. Changes in gene expression level were validated using quantitative real-time PCR in PBMCs from patients with sepsis. To further support that the source of the upregulated module of genes\/proteins found in our results were derived from LDNs, we identified an increase of this population by flow cytometry in PBMC samples obtained from the same cohort of septic patients included in the proteomic analysis. This study provides new insights into a reprioritization of biological functions in response to sepsis that involved a transcriptional and translational shutdown of genes\/proteins, with exception of a set of genes\/proteins related to LDNs and host\u2010defense system.<\/jats:p>","DOI":"10.3389\/fimmu.2021.744799","type":"journal-article","created":{"date-parts":[[2021,9,10]],"date-time":"2021-09-10T09:45:04Z","timestamp":1631267104000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":32,"title":["Combined Transcriptome and Proteome Leukocyte\u2019s Profiling Reveals Up-Regulated Module of Genes\/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis"],"prefix":"10.3389","volume":"12","author":[{"given":"Giuseppe Gianini Figueir\u00eado","family":"Leite","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Lima","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre Keiji","family":"Tashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika Sayuri","family":"Nishiduka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edecio","family":"Cunha-Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milena Karina Colo","family":"Brunialti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Murillo","family":"Assuncao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano Cesar Pontes","family":"Azevedo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fl\u00e1vio","family":"Freitas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"van der Poll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendon P.","family":"Scicluna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinaldo","family":"Salom\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,9,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","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":"B2","doi-asserted-by":"publisher","DOI":"10.12688\/f1000research.15758.1","article-title":"Recent Advances in Understanding and Managing Sepsis","volume":"7","author":"Berg","year":"2018","journal-title":"F1000Res"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0b013e318262c4b0","article-title":"Bacterial Sensing, Cell Signaling, and Modulation of the Immune Response During Sepsis","volume":"38","author":"Salomao","year":"2012","journal-title":"Shock"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nri.2017.36","article-title":"The Immunopathology of Sepsis and Potential Therapeutic Targets","volume":"17","author":"van der Poll","year":"2017","journal-title":"Nat Rev Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(13)70001-X","article-title":"Immunosuppression in Sepsis: A Novel Understanding of the Disorder and a New Therapeutic Approach","volume":"13","author":"Hotchkiss","year":"2013","journal-title":"Lancet Infect Dis"},{"key":"B6","doi-asserted-by":"publisher","first-page":"e8595","DOI":"10.1590\/1414-431X20198595","article-title":"Sepsis: Evolving Concepts and Challenges","volume":"52","author":"Salom\u00e3o","year":"2019","journal-title":"Braz J Med Biol Res"},{"key":"B7","doi-asserted-by":"publisher","first-page":"15606","DOI":"10.1038\/s41598-017-15755-1","article-title":"Proteomic Study Revealed Cellular Assembly and Lipid Metabolism Dysregulation in Sepsis Secondary to Community-Acquired Pneumonia","volume":"7","author":"Sharma","year":"2017","journal-title":"Sci Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111354","article-title":"A Genomic Storm in Critically Injured Humans","volume":"208","author":"Xiao","year":"2011","journal-title":"J Exp Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-2600(17)30294-1","article-title":"Classification of Patients With Sepsis According to Blood Genomic Endotype: A Prospective Cohort Study","volume":"5","author":"Scicluna","year":"2017","journal-title":"Lancet Respir Med"},{"key":"B10","doi-asserted-by":"publisher","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":"B11","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201608-1685OC","article-title":"Shared and Distinct Aspects of the Sepsis Transcriptomic Response to Fecal Peritonitis and Pneumonia","volume":"196","author":"Burnham","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jinf.2014.12.010","article-title":"Transcriptomic Correlates of Organ Failure Extent in Sepsis","volume":"70","author":"Almansa","year":"2015","journal-title":"J Infect"},{"key":"B13","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41540-019-0105-4","article-title":"Genetic Signature Related to Heme-Hemoglobin Metabolism Pathway in Sepsis Secondary to Pneumonia","volume":"5","author":"Leite","year":"2019","journal-title":"NPJ Syst Biol Appl"},{"key":"B14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1186\/s12014-019-9252-2","article-title":"Lipid Metabolism Impairment in Patients With Sepsis Secondary to Hospital Acquired Pneumonia, a Proteomic Analysis","volume":"16","author":"Sharma","year":"2019","journal-title":"Clin Proteomics"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.12659\/msm.918491","article-title":"Bioinformatics Analysis of Gene Expression Profiles for Risk Prediction in Patients With Septic Shock","volume":"25","author":"Hu","year":"2019","journal-title":"Med Sci Monit"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e920818","DOI":"10.12659\/msm.920818","article-title":"Bioinformatics Analysis for Multiple Gene Expression Profiles in Sepsis","volume":"26","author":"Zhai","year":"2020","journal-title":"Med Sci Monit"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e16807","DOI":"10.1097\/md.0000000000016807","article-title":"Identifying Crucial Genes for Prognosis in Septic Patients: Gene Integration Study Based on PRISMA Guidelines","volume":"98","author":"Hu","year":"2019","journal-title":"Medicine"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.4A0219-050R","article-title":"Leukocyte Transcriptional Signatures Dependent on LPS Dosage in Human Endotoxemia","volume":"106","author":"Khan","year":"2019","journal-title":"J Leukoc Biol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1378\/chest.101.6.1644","article-title":"Definitions for Sepsis and Organ Failure and Guidelines for the Use of Innovative Therapies in Sepsis. The ACCP\/SCCM Consensus Conference Committee. American College of Chest Physicians\/Society of Critical Care Medicine","volume":"101","author":"Bone","year":"1992","journal-title":"Chest"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1976.9999","article-title":"A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal Biochem"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2767","article-title":"Drift Time-Specific Collision Energies Enable Deep-Coverage Data-Independent Acquisition Proteomics","volume":"11","author":"Distler","year":"2014","journal-title":"Nat Methods"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.6b00923","article-title":"Intrauterine Growth Restriction Programs the Hypothalamus of Adult Male Rats: Integrated Analysis of Proteomic and Metabolomic Data","volume":"16","author":"Pedroso","year":"2017","journal-title":"J\u00a0Proteome Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.jprot.2016.07.012","article-title":"Peptidomics of Acanthoscurria Gomesiana Spider Venom Reveals New Toxins With Potential Antimicrobial Activity","volume":"151","author":"Abreu","year":"2017","journal-title":"J Proteomics"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2020.01075","article-title":"A Multiomics Approach Unravels New Toxins With Possible In Silico Antimicrobial, Antiviral, and Antitumoral Activities in the Venom of Acanthoscurria Rondoniae","volume":"11","author":"C\u00e2mara","year":"2020","journal-title":"Front Pharmacol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M500230-MCP200","article-title":"Absolute Quantification of Proteins by LCMSE: A Virtue of Parallel MS Acquisition","volume":"5","author":"Silva","year":"2006","journal-title":"Mol Cell Proteomics"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3901","article-title":"The Perseus Computational Platform for Comprehensive Analysis of (Prote)Omics Data","volume":"13","author":"Tyanova","year":"2016","journal-title":"Nat Methods"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3390\/life11040359","article-title":"A Comparative Analysis of Erythropoietin and Carbamoylated Erythropoietin Proteome Profiles","volume":"11","author":"Tiwari","year":"2021","journal-title":"Life"},{"key":"B28","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1186\/s40478-018-0524-2","article-title":"Integrated Proteomics and Network Analysis Identifies Protein Hubs and Network Alterations in Alzheimer\u2019s Disease","volume":"6","author":"Zhang","year":"2018","journal-title":"Acta Neuropathol Commun"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.12688\/f1000research.22280.2","article-title":"Visualize Omics Data on Networks With Omics Visualizer, A Cytoscape App","volume":"9","author":"Legeay","year":"2020","journal-title":"F1000Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.8b00702","article-title":"Cytoscape Stringapp: Network Analysis and Visualization of Proteomics Data","volume":"18","author":"Doncheva","year":"2019","journal-title":"J Proteome Res"},{"key":"B31","doi-asserted-by":"publisher","first-page":"e1008239","DOI":"10.1371\/journal.pcbi.1008239","article-title":"Multiscale Community Detection in Cytoscape","volume":"16","author":"Singhal","year":"2020","journal-title":"PloS Comput Biol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1186\/s12865-017-0223-y","article-title":"Selection of Reliable Reference Genes for the Normalisation of Gene Expression Levels Following Time Course LPS Stimulation of Murine Bone Marrow Derived Macrophages","volume":"18","author":"Tanaka","year":"2017","journal-title":"BMC Immunol"},{"key":"B33","unstructured":"Reference Genes for Quantitative Qpcr Analyses in Monocytes of Septic Patients\n            GritteRB\n            Souza-SiqueiraT\n            MaisLN\n          2020"},{"key":"B34","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.medj.2020.07.002","article-title":"Virus-Host Interactome and Proteomic Survey Reveal Potential Virulence Factors Influencing SARS-Cov-2 Pathogenesis","volume":"2","author":"Li","year":"2021","journal-title":"Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jproteome.7b00476","article-title":"Proteomic Analysis of Peripheral Blood Mononuclear Cells After a High-Fat, High-Carbohydrate Meal With Orange Juice","volume":"16","author":"Chaves","year":"2017","journal-title":"J Proteome Res"},{"key":"B36","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1016\/j.jprot.2015.05.033","article-title":"Label-Free Proteomic Analysis of Pbmcs Reveals Gender Differences in Response to Long-Term Antiretroviral Therapy of HIV","volume":"126","author":"Zhang","year":"2015","journal-title":"J Proteomics"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1212622","article-title":"Sharma J. C-Type Lectin Receptor Clec4d Plays a Protective Role in Resolution of Gram-Negative Pneumonia","volume":"94","author":"Steichen","year":"2013","journal-title":"J Leukoc Biol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-0572-6","article-title":"Expansion of Myeloid-Derived Suppressor Cells in Patients With Severe Coronavirus Disease (COVID-19)","volume":"27","author":"Agrati","year":"2020","journal-title":"Cell Death Differ"},{"key":"B39","doi-asserted-by":"publisher","first-page":"e148435","DOI":"10.1172\/jci.insight.148435","article-title":"A Specific Low-Density Neutrophil Population Correlates With Hypercoagulation and Disease Severity in Hospitalized COVID-19 Patients","volume":"6","author":"Morrissey","year":"2021","journal-title":"JCI Insight"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0153567","article-title":"Low-Density Granulocytes are Elevated in Mycobacterial Infection and Associated With the Severity of Tuberculosis","volume":"11","author":"Deng","year":"2016","journal-title":"PloS One"},{"key":"B41","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1016\/j.chom.2017.10.011","article-title":"Multi-Platform 'Omics Analysis of Human Ebola Virus Disease Pathogenesis","volume":"22","author":"Eisfeld","year":"2017","journal-title":"Cell Host Microbe"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1186\/cc14003","article-title":"Neutrophils With Myeloid Derived Suppressor Function Deplete Arginine and Constrain T Cell Function in Septic Shock Patients","volume":"18","author":"Darcy","year":"2014","journal-title":"Crit Care"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201606-1143OC","article-title":"Early Expansion of Circulating Granulocytic Myeloid-Derived Suppressor Cells Predicts Development of Nosocomial Infections in Patients With Sepsis","volume":"196","author":"Uhel","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/4745067","article-title":"Endotoxin Engages Mitochondrial Quality Control via an Inos-Reactive Oxygen Species Signaling Pathway in Hepatocytes","volume":"2019","author":"Cyr","year":"2019","journal-title":"Oxid Med Cell Longev"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1186\/s40635-016-0078-1","article-title":"Modulation of Monocytes in Septic Patients: Preserved Phagocytic Activity, Increased ROS and NO Generation, and Decreased Production of Inflammatory Cytokines","volume":"4","author":"Santos","year":"2016","journal-title":"Intensive Care Med Exp"},{"key":"B46","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1111\/imm.12854","article-title":"The Biology of Natural Killer Cells During Sepsis","volume":"153","author":"Guo","year":"2018","journal-title":"Immunology"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/986491","article-title":"The Role of Natural Killer Cells in Sepsis","volume":"2011","author":"Chiche","year":"2011","journal-title":"J BioMed Biotechnol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0210850","article-title":"Combined Transcriptomics and Proteomics Forecast Analysis for Potential Genes Regulating the Columbian Plumage Color in Chickens","volume":"14","author":"Wang","year":"2019","journal-title":"PloS One"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/18.4.585","article-title":"Analysis of Mrna Expression and Protein Abundance Data: An Approach for the Comparison of the Enrichment of Features in the Cellular Population of Proteins and Transcripts","volume":"18","author":"Greenbaum","year":"2002","journal-title":"Bioinformatics"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.ecoenv.2021.112271","article-title":"Proteomics and Transcriptomics Jointly Identify the Key Role of Oxidative Phosphorylation in Fluoride-Induced Myocardial Mitochondrial Dysfunction in Rats","volume":"218","author":"Xie","year":"2021","journal-title":"Ecotoxicol Environ Saf"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e239","DOI":"10.1002\/fes3.239","article-title":"Integrated Proteome and Transcriptome Analyses Revealed Key Factors Involved in Tomato (Solanum Lycopersicum) Under High Temperature Stress","volume":"9","author":"Ding","year":"2020","journal-title":"Food Energy Secur"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2020.551495","article-title":"Systematic Identification of Hub Genes in Placenta Accreta Spectrum Based on Integrated Transcriptomic and Proteomic Analysis","volume":"11","author":"Chen","year":"2020","journal-title":"Front Genet"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.00576","article-title":"Integrated Transcriptomic and Proteomic Analyses of the Interaction Between Chicken Synovial Fibroblasts and Mycoplasma Synoviae","volume":"11","author":"Liu","year":"2020","journal-title":"Front Microbiol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.652470","article-title":"Neutrophils in COVID-19","volume":"12","author":"Reusch","year":"2021","journal-title":"Front Immunol"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02536","article-title":"Damps and Nets in Sepsis","volume":"10","author":"Denning","year":"2019","journal-title":"Front Immunol"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000002102","article-title":"Olfactomedin-4 Is a Candidate Marker for a Pathogenic Neutrophil Subset in Septic Shock","volume":"45","author":"Alder","year":"2017","journal-title":"Crit\u00a0Care Med"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1038\/227561a0","article-title":"Central Dogma of Molecular Biology","volume":"227","author":"Crick","year":"1970","journal-title":"Nature"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1016\/j.febslet.2009.10.036","article-title":"Correlation of Mrna and Protein in Complex Biological Samples","volume":"583","author":"Maier","year":"2009","journal-title":"FEBS Lett"},{"key":"B59","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.semcdb.2004.11.004","article-title":"Eif2 and the Control of Cell Physiology","volume":"16","author":"Proud","year":"2005","journal-title":"Semin Cell Dev Biol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a032870","article-title":"Role of Eif2\u03b1 Kinases in Translational Control and Adaptation to Cellular Stress","volume":"10","author":"Wek","year":"2018","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"B61","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1172\/JCI123284","article-title":"Bacterial Sepsis Triggers an Antiviral Response That Causes Translation Shutdown","volume":"129","author":"Hato","year":"2019","journal-title":"J Clin Invest"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1038\/nature03985","article-title":"A Network-Based Analysis of Systemic Inflammation in Humans","volume":"437","author":"Calvano","year":"2005","journal-title":"Nature"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2015.03.013","article-title":"The 55S Mammalian Mitochondrial Ribosome and Its Trna-Exit Region","volume":"114","author":"Kaushal","year":"2015","journal-title":"Biochimie"},{"key":"B64","doi-asserted-by":"publisher","first-page":"66","DOI":"10.4161\/viru.26907","article-title":"The Role of Mitochondrial Dysfunction in Sepsis-Induced Multi-Organ Failure","volume":"5","author":"Singer","year":"2014","journal-title":"Virulence"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.744799\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T07:14:30Z","timestamp":1631603670000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.744799\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,10]]},"references-count":64,"alternative-id":["10.3389\/fimmu.2021.744799"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.744799","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,10]]},"article-number":"744799"}}