{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:39:15Z","timestamp":1791279555158,"version":"4.1.0"},"reference-count":88,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003246","name":"NWO","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003246","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["clinicalkey.com","clinicalkey.com.au","clinicalkey.es","clinicalkey.fr","clinicalkey.jp","criticalcare.theclinics.com","theclinics.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Critical Care Clinics"],"published-print":{"date-parts":[[2026,6]]},"DOI":"10.1016\/j.ccc.2026.05.010","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T19:52:46Z","timestamp":1781725966000},"update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immunosuppression in the Pathophysiology of Sepsis"],"prefix":"10.1016","author":[{"given":"Tristan","family":"Couwenbergh","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wouter A.","family":"van der Heijden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mihai G.","family":"Netea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"8","key":"10.1016\/j.ccc.2026.05.010_bib1","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"},{"issue":"11","key":"10.1016\/j.ccc.2026.05.010_bib2","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.1016\/j.immuni.2021.10.012","article-title":"The immunology of sepsis","volume":"54","author":"van der Poll","year":"2021","journal-title":"Immunity"},{"issue":"23","key":"10.1016\/j.ccc.2026.05.010_bib3","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1001\/jama.2011.1829","article-title":"Immunosuppression in patients who die of sepsis and multiple organ failure","volume":"306","author":"Boomer","year":"2011","journal-title":"JAMA"},{"issue":"4","key":"10.1016\/j.ccc.2026.05.010_bib4","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1097\/CCM.0000000000007089","article-title":"Surviving sepsis campaign: international guidelines for management of sepsis and septic shock 2026","volume":"54","author":"Prescott","year":"2026","journal-title":"Crit Care Med"},{"issue":"10","key":"10.1016\/j.ccc.2026.05.010_bib6","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1007\/s00134-025-08110-w","article-title":"Monocyte HLA-DR expression in septic shock patients: insights from a 20-year real-world cohort of 1023 cases","volume":"51","author":"Monneret","year":"2025","journal-title":"Intensive Care Med"},{"issue":"5","key":"10.1016\/j.ccc.2026.05.010_bib7","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1186\/cc5055","article-title":"Bench-to-bedside review: endotoxin tolerance as a model of leukocyte reprogramming in sepsis","volume":"10","author":"Cavaillon","year":"2006","journal-title":"Crit Care"},{"issue":"10","key":"10.1016\/j.ccc.2026.05.010_bib8","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.it.2009.07.009","article-title":"Endotoxin tolerance: new mechanisms, molecules and clinical significance","volume":"30","author":"Biswas","year":"2009","journal-title":"Trends Immunol"},{"key":"10.1016\/j.ccc.2026.05.010_bib9","article-title":"Sepsis-induced immunosuppression: mechanisms, biomarkers and immunotherapy","volume":"16","author":"Gao","year":"2025","journal-title":"Front Immunol"},{"issue":"4","key":"10.1016\/j.ccc.2026.05.010_bib10","doi-asserted-by":"crossref","DOI":"10.1186\/cc7969","article-title":"Phenotype changes and impaired function of dendritic cell subsets in patients with sepsis: a prospective observational analysis","volume":"13","author":"Poehlmann","year":"2009","journal-title":"Crit Care"},{"issue":"1\u20132","key":"10.1016\/j.ccc.2026.05.010_bib11","doi-asserted-by":"crossref","first-page":"64","DOI":"10.2119\/2007-00102.Monneret","article-title":"Monitoring immune dysfunctions in the septic patient: a new skin for the old ceremony","volume":"14","author":"Monneret","year":"2008","journal-title":"Mol Med"},{"issue":"9","key":"10.1016\/j.ccc.2026.05.010_bib12","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1001\/jama.2025.24175","article-title":"Precision immunotherapy to improve sepsis outcomes: the immunosep randomized clinical trial","volume":"335","author":"Giamarellos-Bourboulis","year":"2026","journal-title":"JAMA"},{"issue":"11","key":"10.1016\/j.ccc.2026.05.010_bib13","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.1007\/s00134-010-1962-x","article-title":"Low monocyte human leukocyte antigen-DR is independently associated with nosocomial infections after septic shock","volume":"36","author":"Landelle","year":"2010","journal-title":"Intensive Care Med"},{"issue":"8","key":"10.1016\/j.ccc.2026.05.010_bib14","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1007\/s00134-006-0204-8","article-title":"Persisting low monocyte human leukocyte antigen-DR expression predicts mortality in septic shock","volume":"32","author":"Monneret","year":"2006","journal-title":"Intensive Care Med"},{"key":"10.1016\/j.ccc.2026.05.010_bib15","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2019.00327","article-title":"Myeloid-derived suppressor cells in sepsis. mini review","volume":"10","author":"Schrijver","year":"2019","journal-title":"Front Immunol"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib16","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1158\/2326-6066.CIR-16-0297","article-title":"Myeloid-derived suppressor cells","volume":"5","author":"Gabrilovich","year":"2017","journal-title":"Cancer Immunol Res"},{"issue":"4","key":"10.1016\/j.ccc.2026.05.010_bib17","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1097\/SLA.0000000000001783","article-title":"Human myeloid-derived suppressor cells are associated with chronic immune suppression after severe sepsis\/septic shock","volume":"265","author":"Mathias","year":"2017","journal-title":"Ann Surg"},{"issue":"3","key":"10.1016\/j.ccc.2026.05.010_bib18","doi-asserted-by":"crossref","first-page":"315","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"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib19","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1186\/s13054-019-2628-x","article-title":"Myeloid-derived suppressor cell function and epigenetic expression evolves over time after surgical sepsis","volume":"23","author":"Hollen","year":"2019","journal-title":"Crit Care"},{"issue":"4","key":"10.1016\/j.ccc.2026.05.010_bib20","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S0002-9610(99)00183-X","article-title":"Selective defects of T lymphocyte function in patients with lethal intraabdominal infection","volume":"178","author":"Heidecke","year":"1999","journal-title":"Am J Surg"},{"issue":"2","key":"10.1016\/j.ccc.2026.05.010_bib21","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1067\/mlc.2000.104306","article-title":"Decreased response to recall antigens is associated with depressed costimulatory receptor expression in septic critically ill patients","volume":"135","author":"Manjuck","year":"2000","journal-title":"J Lab Clin Med"},{"issue":"12","key":"10.1016\/j.ccc.2026.05.010_bib22","doi-asserted-by":"crossref","first-page":"2836","DOI":"10.1097\/01.CCM.0000189745.66585.AE","article-title":"Both percentage of gammadelta T lymphocytes and CD3 expression are reduced during septic shock","volume":"33","author":"Venet","year":"2005","journal-title":"Crit Care Med"},{"issue":"5","key":"10.1016\/j.ccc.2026.05.010_bib23","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/SHK.0000000000000234","article-title":"Persistent lymphopenia after diagnosis of sepsis predicts mortality","volume":"42","author":"Drewry","year":"2014","journal-title":"Shock"},{"issue":"8","key":"10.1016\/j.ccc.2026.05.010_bib24","doi-asserted-by":"crossref","first-page":"5110","DOI":"10.4049\/jimmunol.174.8.5110","article-title":"Accelerated lymphocyte death in sepsis occurs by both the death receptor and mitochondrial pathways","volume":"174","author":"Hotchkiss","year":"2005","journal-title":"J Immunol"},{"issue":"7","key":"10.1016\/j.ccc.2026.05.010_bib25","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"},{"issue":"3","key":"10.1016\/j.ccc.2026.05.010_bib26","doi-asserted-by":"crossref","first-page":"810","DOI":"10.1097\/CCM.0b013e318274645f","article-title":"Reduction of immunocompetent T cells followed by prolonged lymphopenia in severe sepsis in the elderly","volume":"41","author":"Inoue","year":"2013","journal-title":"Crit Care Med"},{"key":"10.1016\/j.ccc.2026.05.010_bib27","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2023.1130009","article-title":"Sepsis-induced changes in differentiation, maintenance, and function of memory CD8 T cell subsets","volume":"14","author":"Heidarian","year":"2023","journal-title":"Front Immunol"},{"issue":"5","key":"10.1016\/j.ccc.2026.05.010_bib28","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1097\/CCM.0000000000002380","article-title":"Activation-associated accelerated apoptosis of memory b cells in critically ill patients with sepsis","volume":"45","author":"Shankar-Hari","year":"2017","journal-title":"Crit Care Med"},{"issue":"2","key":"10.1016\/j.ccc.2026.05.010_bib29","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1056\/NEJMra021333","article-title":"The pathophysiology and treatment of sepsis","volume":"348","author":"Hotchkiss","year":"2003","journal-title":"N Engl J Med"},{"issue":"6","key":"10.1016\/j.ccc.2026.05.010_bib30","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1097\/01.CCM.0000063579.43470.AA","article-title":"Depressed interleukin-12-producing activity by monocytes correlates with adverse clinical course and a shift toward Th2-type lymphocyte pattern in severely injured male trauma patients","volume":"31","author":"Spolarics","year":"2003","journal-title":"Crit Care Med"},{"issue":"4","key":"10.1016\/j.ccc.2026.05.010_bib31","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1097\/00000658-199522240-00006","article-title":"Major injury leads to predominance of the T helper-2 lymphocyte phenotype and diminished interleukin-12 production associated with decreased resistance to infection","volume":"222","author":"O'Sullivan","year":"1995","journal-title":"Ann Surg"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib32","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12967-019-1811-9","article-title":"Early and dynamic alterations of Th2\/Th1 in previously immunocompetent patients with community-acquired severe sepsis: a prospective observational study","volume":"17","author":"Xue","year":"2019","journal-title":"J Transl Med"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib33","doi-asserted-by":"crossref","DOI":"10.1111\/sji.12813","article-title":"Dynamic changes in human HLA-DRA gene expression and Th cell subsets in sepsis: indications of immunosuppression and associated outcomes","volume":"91","author":"Xu","year":"2020","journal-title":"Scand J Immunol"},{"key":"10.1016\/j.ccc.2026.05.010_bib34","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1146\/annurev-physiol-061121-040214","article-title":"Sepsis-Induced immunosuppression","volume":"84","author":"Torres","year":"2022","journal-title":"Annu Rev Physiol"},{"issue":"7","key":"10.1016\/j.ccc.2026.05.010_bib35","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1097\/01.CCM.0000069345.78884.0F","article-title":"Marked elevation of human circulating CD4+CD25+ regulatory T cells in sepsis-induced immunoparalysis","volume":"31","author":"Monneret","year":"2003","journal-title":"Crit Care Med"},{"issue":"11","key":"10.1016\/j.ccc.2026.05.010_bib36","doi-asserted-by":"crossref","first-page":"2329","DOI":"10.1097\/01.CCM.0000145999.42971.4B","article-title":"Increased percentage of CD4+CD25+ regulatory T cells during septic shock is due to the decrease of CD4+CD25- lymphocytes","volume":"32","author":"Venet","year":"2004","journal-title":"Crit Care Med"},{"issue":"12","key":"10.1016\/j.ccc.2026.05.010_bib37","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"},{"issue":"9","key":"10.1016\/j.ccc.2026.05.010_bib38","doi-asserted-by":"crossref","first-page":"6540","DOI":"10.4049\/jimmunol.177.9.6540","article-title":"Human CD4+CD25+ regulatory T lymphocytes inhibit lipopolysaccharide-induced monocyte survival through a Fas\/Fas ligand-dependent mechanism","volume":"177","author":"Venet","year":"2006","journal-title":"J Immunol"},{"key":"10.1016\/j.ccc.2026.05.010_bib39","doi-asserted-by":"crossref","DOI":"10.3389\/fimmu.2018.01545","article-title":"Regulatory T cells and acute lung injury: cytokines, uncontrolled inflammation, and therapeutic implications. review","volume":"9","author":"Lin","year":"2018","journal-title":"Front Immunol"},{"issue":"4","key":"10.1016\/j.ccc.2026.05.010_bib40","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1164\/rccm.201606-1225OC","article-title":"The host response in patients with sepsis developing intensive care unit-acquired secondary infections","volume":"196","author":"van Vught","year":"2017","journal-title":"Am J Respir Crit Care Med"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib41","doi-asserted-by":"crossref","first-page":"R3","DOI":"10.1186\/cc13176","article-title":"Targeting the programmed cell death 1: programmed cell death ligand 1 pathway reverses T cell exhaustion in patients with sepsis","volume":"18","author":"Chang","year":"2014","journal-title":"Crit Care"},{"issue":"2","key":"10.1016\/j.ccc.2026.05.010_bib42","doi-asserted-by":"crossref","first-page":"R99","DOI":"10.1186\/cc10112","article-title":"Programmed death-1 levels correlate with increased mortality, nosocomial infection and immune dysfunctions in septic shock patients","volume":"15","author":"Guignant","year":"2011","journal-title":"Crit Care"},{"issue":"9","key":"10.1016\/j.ccc.2026.05.010_bib43","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1007\/s00134-011-2306-1","article-title":"Profound and persistent decrease of circulating dendritic cells is associated with ICU-acquired infection in patients with septic shock","volume":"37","author":"Grimaldi","year":"2011","journal-title":"Intensive Care Med"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib44","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1007\/s00134-006-0436-7","article-title":"Decrease in circulating dendritic cells predicts fatal outcome in septic shock","volume":"33","author":"Guisset","year":"2007","journal-title":"Intensive Care Med"},{"issue":"2","key":"10.1016\/j.ccc.2026.05.010_bib45","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1006\/jsre.1997.5117","article-title":"Inducible macrophage apoptosis following sepsis is mediated by cysteine protease activation and nitric oxide release","volume":"70","author":"Williams","year":"1997","journal-title":"J Surg Res"},{"key":"10.1016\/j.ccc.2026.05.010_bib46","doi-asserted-by":"crossref","first-page":"3967","DOI":"10.2147\/JIR.S426007","article-title":"Advances in the study of immunosuppressive mechanisms in sepsis","volume":"16","author":"Fu","year":"2023","journal-title":"J Inflamm Res"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib47","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1097\/01.shk.0000170353.80318.d5","article-title":"Harmful and protective roles of neutrophils in sepsis","volume":"24","author":"Hoesel","year":"2005","journal-title":"Shock"},{"issue":"8","key":"10.1016\/j.ccc.2026.05.010_bib48","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0072249","article-title":"IFN-\u03b3-stimulated neutrophils suppress lymphocyte proliferation through expression of PD-L1","volume":"8","author":"de Kleijn","year":"2013","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib49","doi-asserted-by":"crossref","first-page":"e77","DOI":"10.1097\/CCM.0000000000002016","article-title":"Suppression of T cell autophagy results in decreased viability and function of t cells through accelerated apoptosis in a murine sepsis model","volume":"45","author":"Oami","year":"2017","journal-title":"Crit Care Med"},{"issue":"12","key":"10.1016\/j.ccc.2026.05.010_bib50","doi-asserted-by":"crossref","first-page":"1906","DOI":"10.1038\/cdd.2016.94","article-title":"Cellular and viral microRNAs in sepsis: mechanisms of action and clinical applications","volume":"23","author":"Giza","year":"2016","journal-title":"Cell Death Differ"},{"issue":"7","key":"10.1016\/j.ccc.2026.05.010_bib51","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":"van der Poll","year":"2017","journal-title":"Nat Rev Immunol"},{"issue":"3","key":"10.1016\/j.ccc.2026.05.010_bib52","doi-asserted-by":"crossref","first-page":"328","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"},{"issue":"3","key":"10.1016\/j.ccc.2026.05.010_bib53","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1016\/j.immuni.2015.02.001","article-title":"Human monocytes undergo functional re-programming during sepsis mediated by hypoxia-inducible factor-1\u03b1","volume":"42","author":"Shalova","year":"2015","journal-title":"Immunity"},{"issue":"3","key":"10.1016\/j.ccc.2026.05.010_bib54","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1007\/s00134-003-2118-z","article-title":"Transient Bcl-2 gene down-expression in circulating mononuclear cells of severe sepsis patients who died despite appropriate intensive care","volume":"30","author":"Bilbault","year":"2004","journal-title":"Intensive Care Med"},{"issue":"4","key":"10.1016\/j.ccc.2026.05.010_bib55","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1038\/ni.3398","article-title":"Broad defects in the energy metabolism of leukocytes underlie immunoparalysis in sepsis","volume":"17","author":"Cheng","year":"2016","journal-title":"Nat Immunol"},{"issue":"21","key":"10.1016\/j.ccc.2026.05.010_bib56","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1056\/NEJMoa2215145","article-title":"Hydrocortisone in severe community-acquired pneumonia","volume":"388","author":"Dequin","year":"2023","journal-title":"N Engl J Med"},{"issue":"4","key":"10.1016\/j.ccc.2026.05.010_bib57","doi-asserted-by":"crossref","DOI":"10.1186\/cc10332","article-title":"The late phase of sepsis is characterized by an increased microbiological burden and death rate","volume":"15","author":"Otto","year":"2011","journal-title":"Crit Care"},{"issue":"4","key":"10.1016\/j.ccc.2026.05.010_bib58","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1016\/j.coi.2013.05.006","article-title":"Monitoring the immune response in sepsis: a rational approach to administration of immunoadjuvant therapies","volume":"25","author":"Venet","year":"2013","journal-title":"Curr Opin Immunol"},{"issue":"9","key":"10.1016\/j.ccc.2026.05.010_bib59","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1093\/cid\/cix120","article-title":"Epidemiology of multiple herpes viremia in previously immunocompetent patients with septic shock","volume":"64","author":"Ong","year":"2017","journal-title":"Clin Infect Dis"},{"issue":"2","key":"10.1016\/j.ccc.2026.05.010_bib60","article-title":"Reactivation of multiple viruses in patients with sepsis","volume":"9","author":"Walton","year":"2014","journal-title":"PLoS One"},{"key":"10.1016\/j.ccc.2026.05.010_bib61","doi-asserted-by":"crossref","DOI":"10.1016\/j.ebiom.2020.103044","article-title":"Exploring the pathophysiology of post-sepsis syndrome to identify therapeutic opportunities","volume":"61","author":"van der Slikke","year":"2020","journal-title":"EBioMedicine"},{"issue":"6","key":"10.1016\/j.ccc.2026.05.010_bib62","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1161\/CIRCULATIONAHA.111.040766","article-title":"Cardiac complications in patients with community-acquired pneumonia: incidence, timing, risk factors, and association with short-term mortality","volume":"125","author":"Corrales-Medina","year":"2012","journal-title":"Circulation"},{"key":"10.1016\/j.ccc.2026.05.010_bib63","article-title":"Late mortality after sepsis: propensity matched cohort study","volume":"353","author":"Prescott","year":"2016","journal-title":"Br Med J"},{"issue":"3","key":"10.1016\/j.ccc.2026.05.010_bib64","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/TA.0000000000001135","article-title":"The long-term burden of severe sepsis and septic shock: sepsis recidivism and organ dysfunction","volume":"81","author":"Guirgis","year":"2016","journal-title":"J Trauma Acute Care Surg"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib65","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1001\/jama.2017.17687","article-title":"Enhancing recovery from sepsis: a review","volume":"319","author":"Prescott","year":"2018","journal-title":"JAMA"},{"key":"10.1016\/j.ccc.2026.05.010_bib66","article-title":"Immunological endotyping of chronic critical illness after severe sepsis","volume":"7","author":"Fenner","year":"2020","journal-title":"Front Med"},{"issue":"8","key":"10.1016\/j.ccc.2026.05.010_bib67","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1038\/s41590-021-00979-1","article-title":"Epigenetic scars of CD8(+) T cell exhaustion persist after cure of chronic infection in humans","volume":"22","author":"Yates","year":"2021","journal-title":"Nat Immunol"},{"issue":"6","key":"10.1016\/j.ccc.2026.05.010_bib68","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/s41590-020-0673-x","article-title":"Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis","volume":"21","author":"Roquilly","year":"2020","journal-title":"Nat Immunol"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib69","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s13613-017-0304-3","article-title":"Assessment of sepsis-induced immunosuppression at ICU discharge and 6 months after ICU discharge","volume":"7","author":"Zorio","year":"2017","journal-title":"Ann Intensive Care"},{"issue":"8","key":"10.1016\/j.ccc.2026.05.010_bib70","doi-asserted-by":"crossref","DOI":"10.1001\/jamanetworkopen.2019.8686","article-title":"Long-term host immune response trajectories among hospitalized patients with sepsis","volume":"2","author":"Yende","year":"2019","journal-title":"JAMA Netw Open"},{"issue":"3","key":"10.1016\/j.ccc.2026.05.010_bib71","doi-asserted-by":"crossref","first-page":"725","DOI":"10.4049\/jimmunol.1900435","article-title":"Sepsis-induced state of immunoparalysis is defined by diminished CD8 T cell-mediated antitumor immunity","volume":"203","author":"Danahy","year":"2019","journal-title":"J Immunol"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib72","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41420-023-01766-7","article-title":"Immune dysregulation in sepsis: experiences, lessons and perspectives","volume":"9","author":"Cao","year":"2023","journal-title":"Cell Death Discov"},{"key":"10.1016\/j.ccc.2026.05.010_bib73","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1186\/1471-2334-14-166","article-title":"Interferon-gamma as adjunctive immunotherapy for invasive fungal infections: a case series","volume":"14","author":"Delsing","year":"2014","journal-title":"BMC Infect Dis"},{"issue":"5","key":"10.1016\/j.ccc.2026.05.010_bib74","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1038\/s41590-025-02136-4","article-title":"Systemic inflammation impairs myelopoiesis and interferon type I responses in humans","volume":"26","author":"Keramati","year":"2025","journal-title":"Nat Immunol"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib75","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1097\/ALN.0000000000002185","article-title":"Early-phase innate immune suppression in murine severe sepsis is restored with systemic interferon-\u03b2","volume":"129","author":"Kusakabe","year":"2018","journal-title":"Anesthesiology"},{"issue":"3","key":"10.1016\/j.ccc.2026.05.010_bib76","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.4049\/jimmunol.0902307","article-title":"IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis","volume":"184","author":"Inoue","year":"2010","journal-title":"J Immunol"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib77","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1200\/JCO.2014.57.3329","article-title":"Redistribution, hyperproliferation, activation of natural killer cells and CD8 T cells, and cytokine production during first-in-human clinical trial of recombinant human interleukin-15 in patients with cancer","volume":"33","author":"Conlon","year":"2015","journal-title":"J Clin Oncol"},{"issue":"7","key":"10.1016\/j.ccc.2026.05.010_bib78","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1164\/rccm.200903-0363OC","article-title":"Granulocyte-macrophage colony-stimulating factor to reverse sepsis-associated immunosuppression: a double-blind, randomized, placebo-controlled multicenter trial","volume":"180","author":"Meisel","year":"2009","journal-title":"Am J Respir Crit Care Med"},{"issue":"8","key":"10.1016\/j.ccc.2026.05.010_bib79","doi-asserted-by":"crossref","DOI":"10.3390\/jcm10081742","article-title":"Dysregulated immunity and immunotherapy after sepsis","volume":"10","author":"Darden","year":"2021","journal-title":"J Clin Med"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib80","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s13054-016-1301-x","article-title":"Monocyte programmed death ligand-1 expression after 3-4 days of sepsis is associated with risk stratification and mortality in septic patients: a prospective cohort study","volume":"20","author":"Shao","year":"2016","journal-title":"Crit Care"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib81","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1097\/SHK.0b013e3182168cce","article-title":"Dose-dependent effect of anti-CTLA-4 on survival in sepsis","volume":"36","author":"Inoue","year":"2011","journal-title":"Shock"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib82","doi-asserted-by":"crossref","DOI":"10.1186\/cc11932","article-title":"The efficacy of thymosin alpha 1 for severe sepsis (ETASS): a multicenter, single-blind, randomized and controlled trial","volume":"17","author":"Wu","year":"2013","journal-title":"Crit Care"},{"key":"10.1016\/j.ccc.2026.05.010_bib83","doi-asserted-by":"crossref","DOI":"10.1136\/bmj-2024-082583","article-title":"The efficacy and safety of thymosin \u03b11 for sepsis (TESTS): Multicentre, double blinded, randomised, placebo controlled, phase 3 trial","volume":"388","author":"Wu","year":"2025","journal-title":"Br Med J"},{"issue":"15","key":"10.1016\/j.ccc.2026.05.010_bib84","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1089\/ars.2021.0005","article-title":"Targeting toll-like receptors in sepsis: from bench to clinical trials","volume":"35","author":"Chen","year":"2021","journal-title":"Antioxid Redox Signaling"},{"issue":"6","key":"10.1016\/j.ccc.2026.05.010_bib85","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/82741","article-title":"Caspase inhibitors improve survival in sepsis: a critical role of the lymphocyte","volume":"1","author":"Hotchkiss","year":"2000","journal-title":"Nat Immunol"},{"issue":"9","key":"10.1016\/j.ccc.2026.05.010_bib86","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/s41551-023-01050-0","article-title":"Resolving sepsis-induced immunoparalysis via trained immunity by targeting interleukin-4 to myeloid cells","volume":"7","author":"Schrijver","year":"2023","journal-title":"Nat Biomed Eng"},{"key":"10.1016\/j.ccc.2026.05.010_bib87","doi-asserted-by":"crossref","DOI":"10.1155\/2015\/261864","article-title":"Gamma-irradiated bacille calmette-Gu\u00e9rin vaccination does not modulate the innate immune response during experimental human endotoxemia in adult males","volume":"2015","author":"Hamers","year":"2015","journal-title":"J Immunol Res"},{"issue":"12","key":"10.1016\/j.ccc.2026.05.010_bib88","doi-asserted-by":"crossref","first-page":"4119","DOI":"10.1038\/s41591-025-03964-5","article-title":"A consensus blood transcriptomic framework for sepsis","volume":"31","author":"Scicluna","year":"2025","journal-title":"Nat Med"},{"issue":"1","key":"10.1016\/j.ccc.2026.05.010_bib89","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s00134-025-08218-z","article-title":"Temporal robustness of biomarker-based classification algorithms for sepsis","volume":"52","author":"Rademaker","year":"2026","journal-title":"Intensive Care Med"}],"container-title":["Critical Care Clinics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0749070426000394?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0749070426000394?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T18:14:10Z","timestamp":1782152050000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0749070426000394"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6]]},"references-count":88,"alternative-id":["S0749070426000394"],"URL":"https:\/\/doi.org\/10.1016\/j.ccc.2026.05.010","relation":{},"ISSN":["0749-0704"],"issn-type":[{"value":"0749-0704","type":"print"}],"subject":[],"published":{"date-parts":[[2026,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Immunosuppression in the Pathophysiology of Sepsis","name":"articletitle","label":"Article Title"},{"value":"Critical Care Clinics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ccc.2026.05.010","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}]}}