{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T07:06:11Z","timestamp":1790406371444,"version":"4.1.0"},"reference-count":62,"publisher":"Portland Press Ltd.","issue":"5","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,9,1]]},"abstract":"<jats:p>Perioperative lymphopenia has been linked with an increased risk of postoperative infectious complications, but the mechanisms remain unclear. We tested the hypothesis that bioenergetic dysfunction is an important mechanism underlying lymphopenia, impaired functionality and infectious complications. In two cohorts of patients (61\u201382\u00a0years old) undergoing orthopaedic joint replacement (n=417 and 328, respectively), we confirmed prospectively that preoperative lymphopenia (\u22641.3 x 109\u00b7l\u22121; &amp;lt;20% white cell count; prevalence 15\u201318%) was associated with infectious complications (relative risk 1.5 (95% confidence interval 1.1\u20132.0); P=0.008) and prolonged hospital stay. Lymphocyte respirometry, mitochondrial bioenergetics and function were assessed (n=93 patients). Postoperative lymphocytes showed a median 43% fall (range: 26\u201365%; P=0.029; n=13 patients) in spare respiratory capacity, the extra capacity available to produce energy in response to stress. This was accompanied by reduced glycolytic capacity. A similar hypometabolic phenotype was observed in lymphocytes sampled preoperatively from chronically lymphopenic patients (n=21). This hypometabolic phenotype was associated with functional lymphocyte impairment including reduced T-cell proliferation, lower intracellular cytokine production and excess apoptosis induced by a range of common stressors. Glucocorticoids, which are ubiquitously elevated for a prolonged period postoperatively, generated increased levels of mitochondrial reactive oxygen species, activated caspase-1 and mature interleukin (IL)-1\u03b2 in human lymphocytes, suggesting inflammasome activation. mRNA transcription of the NLRP1 inflammasome was increased in lymphocytes postoperatively. Genetic ablation of the murine NLRP3 inflammasome failed to prevent glucocorticoid-induced lymphocyte apoptosis and caspase-1 activity, but increased NLRP1 protein expression. Our findings suggest that the hypometabolic phenotype observed in chronically lymphopenic patients and\/or acquired postoperatively increases the risk of postoperative infection through glucocorticoid activation of caspase-1 via the NLRP1 inflammasome.<\/jats:p>","DOI":"10.1042\/cs20150024","type":"journal-article","created":{"date-parts":[[2015,4,22]],"date-time":"2015-04-22T11:11:58Z","timestamp":1429701118000},"page":"423-437","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Metabolic dysfunction in lymphocytes promotes postoperative morbidity"],"prefix":"10.1042","volume":"129","author":[{"given":"Mark\u00a0R.","family":"Edwards","sequence":"first","affiliation":[{"name":"Clinical Physiology, Department of Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pervez","family":"Sultan","sequence":"additional","affiliation":[{"name":"Clinical Physiology, Department of Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana\u00a0Gutierrez","family":"del Arroyo","sequence":"additional","affiliation":[{"name":"Clinical Physiology, Department of Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Whittle","sequence":"additional","affiliation":[{"name":"Clinical Physiology, Department of Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shamir\u00a0N.","family":"Karmali","sequence":"additional","affiliation":[{"name":"Clinical Physiology, Department of Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.\u00a0Ramani","family":"Moonesinghe","sequence":"additional","affiliation":[{"name":"Clinical Physiology, Department of Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fares\u00a0S.","family":"Haddad","sequence":"additional","affiliation":[{"name":"Clinical Physiology, Department of Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael\u00a0G.","family":"Mythen","sequence":"additional","affiliation":[{"name":"Clinical Physiology, Department of Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mervyn","family":"Singer","sequence":"additional","affiliation":[{"name":"Clinical Physiology, Department of Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gareth\u00a0L.","family":"Ackland","sequence":"additional","affiliation":[{"name":"Clinical Physiology, Department of Medicine, University College London, London WC1E 6BT, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2015,6,11]]},"reference":[{"key":"2021113010372456500_B1","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1056\/NEJMcibr1004371","article-title":"Immunotherapy for sepsis\u2013a new approach against an ancient foe","volume":"363","author":"Hotchkiss","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"2021113010372456500_B2","doi-asserted-by":"publisher","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."},{"key":"2021113010372456500_B3","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1038\/nm1207-1409","article-title":"Adaptive immune cells temper initial innate responses","volume":"13","author":"Kim","year":"2007","journal-title":"Nat. Med."},{"key":"2021113010372456500_B4","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1038\/nm1007-1142b","article-title":"Not so fast: adaptive suppression of innate immunity","volume":"13","author":"Palm","year":"2007","journal-title":"Nat. Med."},{"key":"2021113010372456500_B5","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1189\/jlb.5MR0114-067R","article-title":"Impact of sepsis on CD4 T cell immunity","volume":"96","author":"Cabrera-Perez","year":"2014","journal-title":"J. Leukoc. Biol."},{"key":"2021113010372456500_B6","doi-asserted-by":"publisher","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"},{"key":"2021113010372456500_B7","doi-asserted-by":"publisher","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"},{"key":"2021113010372456500_B8","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/nri1710","article-title":"Fuel feeds function: energy metabolism and the T-cell response","volume":"5","author":"Fox","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"2021113010372456500_B9","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1159\/000362502","article-title":"Mitochondrial metabolism in T cell activation and senescence: a mini-review","volume":"61","author":"Ron-Harel","year":"2015","journal-title":"Gerontology."},{"key":"2021113010372456500_B10","doi-asserted-by":"publisher","first-page":"1242454","DOI":"10.1126\/science.1242454","article-title":"Fueling immunity: insights into metabolism and lymphocyte function","volume":"342","author":"Pearce","year":"2013","journal-title":"Science"},{"key":"2021113010372456500_B11","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1038\/nature08100","article-title":"T cells dampen innate immune responses through inhibition of NLRP1 and NLRP3 inflammasomes","volume":"460","author":"Guarda","year":"2009","journal-title":"Nature"},{"key":"2021113010372456500_B12","doi-asserted-by":"publisher","first-page":"10408","DOI":"10.1073\/pnas.0508961103","article-title":"CD4+ T cells and CXC chemokines modulate the pathogenesis of Staphylococcus aureus wound infections","volume":"103","author":"McLoughlin","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010372456500_B13","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.1097\/SLA.0b013e3181bef697","article-title":"Complications, failure to rescue, and mortality with major inpatient surgery in medicare patients","volume":"250","author":"Ghaferi","year":"2009","journal-title":"Ann. Surg."},{"key":"2021113010372456500_B14","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1213\/00000539-199908000-00050","article-title":"The use of a postoperative morbidity survey to evaluate patients with prolonged hospitalization after routine, moderate-risk, elective surgery","volume":"89","author":"Bennett-Guerrero","year":"1999","journal-title":"Anesth. Analg."},{"key":"2021113010372456500_B15","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1213\/ANE.0b013e31825b6824","article-title":"Trends in in-hospital major morbidity and mortality after total joint arthroplasty: United States 1998\u20132008","volume":"115","author":"Kirksey","year":"2012","journal-title":"Anesth. Analg."},{"key":"2021113010372456500_B16","doi-asserted-by":"publisher","first-page":"1375","DOI":"10.1213\/ANE.0b013e3181ee8456","article-title":"Chronic kidney disease and postoperative morbidity after elective orthopedic surgery","volume":"112","author":"Ackland","year":"2011","journal-title":"Anesth. Analg."},{"key":"2021113010372456500_B17","doi-asserted-by":"publisher","first-page":"e23224","DOI":"10.1371\/journal.pone.0023224","article-title":"Hypertensive patients show delayed wound healing following total hip arthroplasty","volume":"6","author":"Ahmed","year":"2011","journal-title":"PLoS One"},{"key":"2021113010372456500_B18","doi-asserted-by":"publisher","first-page":"506","DOI":"10.1016\/S0736-0266(01)00153-X","article-title":"Predictors of wound infection in hip and knee joint replacement: results from a 20 year surveillance program","volume":"20","author":"Saleh","year":"2002","journal-title":"J. Orthop. Res."},{"key":"2021113010372456500_B19","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1182\/blood.V40.1.77.77","article-title":"Methods for obtaining purified lymphocytes, glass-adherent mononuclear cells, and a population containing both cell types\u00a0from human peripheral blood","volume":"40","author":"Levis","year":"1972","journal-title":"Blood"},{"key":"2021113010372456500_B20","doi-asserted-by":"publisher","first-page":"13064","DOI":"10.1073\/pnas.1120585109","article-title":"Toll-like receptor 4 signaling in T cells promotes autoimmune inflammation","volume":"109","author":"Reynolds","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010372456500_B21","doi-asserted-by":"publisher","first-page":"1400","DOI":"10.1176\/appi.ajp.158.9.1400","article-title":"N-methyl-D-aspartic acid receptor expression in the dorsolateral prefrontal cortex of elderly patients with schizophrenia","volume":"158","author":"Dracheva","year":"2001","journal-title":"Am. J. Psychiatry"},{"key":"2021113010372456500_B22","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/j.immuni.2007.07.008","article-title":"Revving the engine: signal transduction fuels T cell activation","volume":"27","author":"Jones","year":"2007","journal-title":"Immunity"},{"key":"2021113010372456500_B23","doi-asserted-by":"publisher","first-page":"14336","DOI":"10.1073\/pnas.1221740110","article-title":"CD8 memory T cells have a bioenergetic advantage that underlies their rapid recall ability","volume":"110","author":"van der Windt","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010372456500_B24","doi-asserted-by":"publisher","first-page":"1239","DOI":"10.1016\/j.cell.2013.05.016","article-title":"Posttranscriptional control of T cell effector function by aerobic glycolysis","volume":"153","author":"Chang","year":"2013","journal-title":"Cell"},{"key":"2021113010372456500_B25","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/S0092-8674(00)81874-7","article-title":"Apoptosis by death factor","volume":"88","author":"Nagata","year":"1997","journal-title":"Cell"},{"key":"2021113010372456500_B26","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1146\/annurev.cellbio.15.1.113","article-title":"Lymphocyte survival\u2013the struggle against death","volume":"15","author":"Arch","year":"1999","journal-title":"Annu. Rev. Cell Dev. Biol."},{"key":"2021113010372456500_B27","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/ncprheum0898","article-title":"Genomic and nongenomic effects of glucocorticoids","volume":"4","author":"Stahn","year":"2008","journal-title":"Nat. Clin. Pract. Rheumatol."},{"key":"2021113010372456500_B28","doi-asserted-by":"publisher","first-page":"426","DOI":"10.1097\/00000542-199209000-00004","article-title":"Responses of plasma adrenocorticotropic hormone, cortisol, and cytokines during and after upper abdominal surgery","volume":"77","author":"Naito","year":"1992","journal-title":"Anesthesiology"},{"key":"2021113010372456500_B29","doi-asserted-by":"publisher","first-page":"36321","DOI":"10.1074\/jbc.M708182200","article-title":"The caspase-1 digestome identifies the glycolysis pathway as a target during infection and septic shock","volume":"282","author":"Shao","year":"2007","journal-title":"J. Biol. Chem."},{"key":"2021113010372456500_B30","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1038\/nature12940","article-title":"Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection","volume":"505","author":"Doitsh","year":"2014","journal-title":"Nature."},{"key":"2021113010372456500_B31","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1093\/bja\/aet077","article-title":"Dynamic output and control of the hypothalamic-pituitary-adrenal axis in critical illness and major surgery","volume":"111","author":"Gibbison","year":"2013","journal-title":"Br. J. Anaesth."},{"key":"2021113010372456500_B32","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1369\/jhc.6A7101.2006","article-title":"Inflammasome components NALP 1 and 3 show distinct but separate expression profiles in human tissues suggesting a site-specific role in the inflammatory response","volume":"55","author":"Kummer","year":"2007","journal-title":"J. Histochem. Cytochem."},{"key":"2021113010372456500_B33","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1016\/j.immuni.2013.05.016","article-title":"K(+) efflux is the common trigger of NLRP3 inflammasome activation by bacterial toxins and particulate matter","volume":"38","author":"Munoz-Planillo","year":"2013","journal-title":"Immunity"},{"key":"2021113010372456500_B34","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/nri2725","article-title":"NLRP3 inflammasome activation: the convergence of multiple signalling pathways on ROS production?","volume":"10","author":"Tschopp","year":"2010","journal-title":"Nat. Rev. Immunol."},{"key":"2021113010372456500_B35","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/S0140-6736(02)09459-X","article-title":"Association between mitochondrial dysfunction and severity and outcome of septic shock","volume":"360","author":"Brealey","year":"2002","journal-title":"Lancet"},{"key":"2021113010372456500_B36","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1042\/CS20140101","article-title":"The Bioenergetic Health Index: a new concept in mitochondrial translational research","volume":"127","author":"Chacko","year":"2014","journal-title":"Clin. Sci."},{"key":"2021113010372456500_B37","doi-asserted-by":"publisher","first-page":"492","DOI":"10.1038\/ni.2035","article-title":"T cell exhaustion","volume":"12","author":"Wherry","year":"2011","journal-title":"Nat. Immunol."},{"key":"2021113010372456500_B38","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1161\/CIRCHEARTFAILURE.112.970525","article-title":"Predictive value of low relative lymphocyte count in patients hospitalized for heart failure with reduced ejection fraction: insights from the EVEREST trial","volume":"5","author":"Vaduganathan","year":"2012","journal-title":"Circ. Heart Fail."},{"key":"2021113010372456500_B39","doi-asserted-by":"publisher","first-page":"c165","DOI":"10.1136\/bmj.c165","article-title":"Relation between hospital orthopaedic specialisation and outcomes in patients aged 65 and older: retrospective analysis of US Medicare data","volume":"340","author":"Hagen","year":"2010","journal-title":"BMJ"},{"key":"2021113010372456500_B40"},{"key":"2021113010372456500_B41","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1056\/NEJMsa0803563","article-title":"Rehospitalizations among patients in the Medicare fee-for-service program","volume":"360","author":"Jencks","year":"2009","journal-title":"N. Engl. J. Med."},{"key":"2021113010372456500_B42","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1016\/j.ahj.2007.06.043","article-title":"Preoperative neutrophil-lymphocyte ratio and outcome from coronary artery bypass grafting","volume":"154","author":"Gibson","year":"2007","journal-title":"Am. Heart J."},{"key":"2021113010372456500_B43","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1097\/00000658-199522240-00011","article-title":"The delayed hypersensitivity response and host resistance in surgical patients. 20\u00a0years later","volume":"222","author":"Christou","year":"1995","journal-title":"Ann. Surg."},{"key":"2021113010372456500_B44","doi-asserted-by":"publisher","first-page":"1037","DOI":"10.1097\/00005373-199806000-00017","article-title":"Both T-helper-1- and T-helper-2-type lymphokines are depressed in posttrauma anergy","volume":"44","author":"Puyana","year":"1998","journal-title":"J. Trauma"},{"key":"2021113010372456500_B45","doi-asserted-by":"publisher","first-page":"794","DOI":"10.1097\/01.CCM.0000256847.61085.A5","article-title":"Negative signaling contributes to T-cell anergy in trauma patients","volume":"35","author":"Bandyopadhyay","year":"2007","journal-title":"Crit. Care Med."},{"key":"2021113010372456500_B46","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1007\/s00134-008-1337-8","article-title":"Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (-)) contribute to lymphocyte anergy in septic shock patients","volume":"35","author":"Venet","year":"2009","journal-title":"Intensive Care Med."},{"key":"2021113010372456500_B47","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/S0140-6736(80)90780-1","article-title":"Prevention of postoperative lymphopenia and granulocytosis by epidural analgesia","volume":"1","author":"Rem","year":"1980","journal-title":"Lancet"},{"key":"2021113010372456500_B48","doi-asserted-by":"publisher","first-page":"R12","DOI":"10.1186\/cc11157","article-title":"Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern","volume":"16","author":"Heffernan","year":"2012","journal-title":"Crit. Care"},{"key":"2021113010372456500_B49","doi-asserted-by":"publisher","first-page":"14541","DOI":"10.1073\/pnas.96.25.14541","article-title":"Prevention of lymphocyte cell death in sepsis improves survival in mice","volume":"96","author":"Hotchkiss","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010372456500_B50","doi-asserted-by":"publisher","first-page":"14541","DOI":"10.1073\/pnas.96.25.14541","article-title":"Prevention of lymphocyte cell death in sepsis improves survival in mice","volume":"96","author":"Hotchkiss","year":"1999","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021113010372456500_B51","doi-asserted-by":"publisher","first-page":"2731","DOI":"10.4049\/jimmunol.172.5.2731","article-title":"Of mice and not men: differences between mouse and human immunology","volume":"172","author":"Mestas","year":"2004","journal-title":"J. Immunol."},{"key":"2021113010372456500_B52","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1097\/01.sla.0000179621.33268.83","article-title":"Determinants of long-term survival after major surgery and the adverse effect of postoperative complications","volume":"242","author":"Khuri","year":"2005","journal-title":"Ann. Surg."},{"key":"2021113010372456500_B53","doi-asserted-by":"publisher","first-page":"67ra68","DOI":"10.1126\/scitranslmed.3001975","article-title":"Manipulating the bioenergetics of alloreactive T cells causes their selective apoptosis and arrests graft-versus-host disease","volume":"3","author":"Gatza","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"2021113010372456500_B54","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1084\/jem.147.2.571","article-title":"A potassium ionophore (Nigericin) inhibits stimulation of human lymphocytes by mitogens","volume":"147","author":"Daniele","year":"1978","journal-title":"J. Exp. Med."},{"key":"2021113010372456500_B55","doi-asserted-by":"publisher","first-page":"38703","DOI":"10.1074\/jbc.M111.275370","article-title":"Glucocorticoids sensitize the innate immune system through regulation of the NLRP3 inflammasome","volume":"286","author":"Busillo","year":"2011","journal-title":"J. Biol. Chem."},{"key":"2021113010372456500_B56","doi-asserted-by":"publisher","first-page":"3701","DOI":"10.1210\/en.2012-1020","article-title":"Proinflammatory actions of glucocorticoids: glucocorticoids and TNFalpha coregulate gene expression in\u00a0vitro and in\u00a0vivo","volume":"153","author":"Lannan","year":"2012","journal-title":"Endocrinology"},{"key":"2021113010372456500_B57","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1182\/blood-2013-03-489468","article-title":"PPARalpha and fatty acid oxidation mediate glucocorticoid resistance in chronic lymphocytic leukemia","volume":"122","author":"Tung","year":"2013","journal-title":"Blood"},{"key":"2021113010372456500_B58","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1097\/MCG.0b013e3181e8ae93","article-title":"Genetic predictors of glucocorticoid response in pediatric patients with inflammatory bowel diseases","volume":"45","author":"De Iudicibus","year":"2011","journal-title":"J. Clin. Gastroenterol."},{"key":"2021113010372456500_B59","doi-asserted-by":"publisher","first-page":"e1003993","DOI":"10.1371\/journal.ppat.1003993","article-title":"Immune suppression by neutrophils in HIV-1 infection: role of PD-L1\/PD-1 pathway","volume":"10","author":"Bowers","year":"2014","journal-title":"PLoS Pathog."},{"key":"2021113010372456500_B60","doi-asserted-by":"publisher","first-page":"260","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":"2021113010372456500_B61","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1172\/JCI57990","article-title":"A subset of neutrophils in human systemic inflammation inhibits T cell responses through Mac-1","volume":"122","author":"Pillay","year":"2012","journal-title":"J. Clin. Invest."},{"key":"2021113010372456500_B62","doi-asserted-by":"publisher","first-page":"4004","DOI":"10.1172\/JCI75051","article-title":"p38 signaling inhibits mTORC1-independent autophagy in senescent human CD8(+) T cells","volume":"124","author":"Henson","year":"2014","journal-title":"J. Clin. Invest."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/129\/5\/423\/443805\/cs1290423.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/129\/5\/423\/443805\/cs1290423.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T06:28:45Z","timestamp":1638253725000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/129\/5\/423\/71246\/Metabolic-dysfunction-in-lymphocytes-promotes"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,6,11]]},"references-count":62,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2015,9,1]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20150024","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,6,11]]}}}