{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T23:28:08Z","timestamp":1790724488569,"version":"4.1.0"},"reference-count":71,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T00:00:00Z","timestamp":1626220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004255","name":"Rajiv Gandhi University of Health Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004255","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Early biomarkers of progression to severe dengue are urgently required to enable effective patient management and control treatment costs. Innate immune cells, which comprise the earliest responders to infection and along with the cytokines and chemokines they secrete, play a vital role in orchestrating the subsequent adaptive immune response and have been implicated in the enhancement of infection and \u201ccytokine storm\u201d associated with dengue severity. We investigated the early innate immune cytokine profile of dengue patients during acute phase of disease in a prospective blinded study that included subjects with acute dengue and febrile controls from four major hospitals in Bengaluru, India along with healthy controls. We used intracellular cytokine staining and flow cytometry to identify innate immune biomarkers that can predict progression to severe dengue.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Dengue infection resulted in enhanced secretion of multiple cytokines by all queried innate immune cell subsets, dominated by TNF-\u03b1 from CD56\n                      <jats:sup>+<\/jats:sup>\n                      CD3\n                      <jats:sup>+<\/jats:sup>\n                      NKT cells, monocyte subsets, and granulocytes along with IFN-\n                      <jats:italic>\u03b3<\/jats:italic>\n                      from CD56\n                      <jats:sup>+<\/jats:sup>\n                      CD3\n                      <jats:sup>+<\/jats:sup>\n                      NKT cells. Of note, significantly higher proportions of TNF-\u03b1 secreting granulocytes and monocyte subsets at admission were associated with mild dengue and minimal symptoms. Dengue NS1 antigenemia used as a surrogate of viral load directly correlated with proportion of cytokine-secreting innate immune cells and was significantly higher in those who went on to recover with minimal symptoms. In patients with secondary dengue or those with bleeding or elevated liver enzymes who revealed predisposition to severe outcomes, early activation as well as efficient downregulation of innate responses were compromised.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our findings suggested that faulty\/delayed kinetics of innate immune activation and downregulation was a driver of disease severity. We identified IFN-\n                      <jats:italic>\u03b3<\/jats:italic>\n                      <jats:sup>+<\/jats:sup>\n                      CD56\n                      <jats:sup>+<\/jats:sup>\n                      CD3\n                      <jats:sup>+<\/jats:sup>\n                      NKT cells and IL-6\n                      <jats:sup>+<\/jats:sup>\n                      granulocytes at admission as novel early biomarkers that can predict the risk of progression to severity (composite AUC = 0.85\u20130.9). Strong correlations among multiple cytokine-secreting innate cell subsets revealed that coordinated early activation of the entire innate immune system in response to dengue virus infection contributed to resolution of infection and speedy recovery.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2021.677874","type":"journal-article","created":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T09:15:53Z","timestamp":1626254153000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Innate Immune Cytokine Profiling and Biomarker Identification for Outcome in Dengue Patients"],"prefix":"10.3389","volume":"12","author":[{"given":"Sai Pallavi","family":"Pradeep","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pooja","family":"Hoovina Venkatesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nageswar R.","family":"Manchala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjun","family":"Vayal Veedu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajani K.","family":"Basavaraju","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leela","family":"Selvasundari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manikanta","family":"Ramakrishna","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogitha","family":"Chandrakiran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishwanath","family":"Krishnamurthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shivaranjani","family":"Holigi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tinku","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecil R.","family":"Ross","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijaya","family":"Satchidanandam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12060","article-title":"The Global Distribution and Burden of Dengue","volume":"496","author":"Bhatt","year":"2013","journal-title":"Nature"},{"key":"B2","article-title":"A Comparison of WHO Guidelines Issued in 1997 and 2009 for Dengue Fever - Single Centre Experience","volume":"63","author":"Khursheed","year":"2013","journal-title":"J Pak Med Assoc"},{"key":"B3","volume-title":"Dengue Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition","author":"World Health","year":"2009"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00035-09","article-title":"Dengue Virus Pathogenesis: An Integrated View","volume":"22","author":"Martina","year":"2009","journal-title":"Clin Microbiol Rev"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1128\/microbiolspec.AID-0022-2014","article-title":"Dengue Antibody-Dependent Enhancement: Knowns and Unknown","volume":"2","author":"Halstead","year":"2014","journal-title":"Microbiol Spectr"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1989.40.444","article-title":"Antibody Dependent Enhancement of Dengue Virus Growth in Human Monocytes as a Risk Factor for Dengue Hemorrhagic Fever","volume":"40","author":"Kliks","year":"1989","journal-title":"Am J Trop Med Hyg"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2008.78.990","article-title":"Influence of the Dengue Serotype, Previous Dengue Infection, and Plasma Viral Load on Clinical Presentation and Outcome During a Dengue-2 and Dengue-4 Co-Epidemic","volume":"78","author":"Thomas","year":"2008","journal-title":"Am J Trop Med Hygiene"},{"key":"B8","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.femsim.2004.11.012","article-title":"Altered T Helper 1 Reaction But Not Increase of Virus Load in Patients With Dengue Hemorrhagic Fever","volume":"44","author":"Chen","year":"2005","journal-title":"FEMS Immunol Med Microbiol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1086\/382280","article-title":"Relationship of Preexisting Dengue Virus (DV) Neutralizing Antibody Levels to Viremia and Severity of Disease in a Prospective Cohort Study of DV Infection in Thailand","volume":"189","author":"Endy","year":"2004","journal-title":"J Infect Dis"},{"key":"B10","article-title":"Viraemia in Patients With Naturally Acquired Dengue Infection","volume":"59","author":"Gubler","year":"1981","journal-title":"Bull World Health Organ"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1086\/340365","article-title":"Differing Influences of Virus Burden and Immune Activation on Disease Severity in Secondary Dengue-3 Virus Infection","volume":"185","author":"Libraty","year":"2002","journal-title":"J Infect Dis"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e2121","DOI":"10.1002\/rmv.2121","article-title":"The Association Between Dengue Viremia Kinetics and Dengue Severity: A Systemic Review and Meta-Analysis","volume":"30","author":"Morsy","year":"2020","journal-title":"Rev Med Virol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1086\/519170","article-title":"Maternal Antibody and Viral Factors in the Pathogenesis of Dengue Virus in Infants","volume":"196","author":"Simmons","year":"2007","journal-title":"J Infect Dis"},{"key":"B14","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1002\/1096-9071(200101)63:1<29::AID-JMV1004>3.0.CO;2-S","article-title":"Analysis of Plasma Viral RNA Levels During Acute Dengue Virus Infection Using Quantitative Competitor Reverse Transcription-Polymerase Chain Reaction","volume":"63","author":"Sudiro","year":"2001","journal-title":"J Med Virol"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1086\/315215","article-title":"Dengue Viremia Titer, Antibody Response Pattern, and Virus Serotype Correlate With Disease Severity","volume":"181","author":"Vaughn","year":"2000","journal-title":"J Infect Dis"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1006\/viro.2002.1704","article-title":"High Levels of Plasma Dengue Viral Load During Defervescence in Patients With Dengue Hemorrhagic Fever: Implications for Pathogenesis","volume":"305","author":"Wang","year":"2003","journal-title":"Virology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1086\/507635","article-title":"Slower Rates of Clearance of Viral Load and Virus-Containing Immune Complexes in Patients With Dengue Hemorrhagic Fever","volume":"43","author":"Wang","year":"2006","journal-title":"Clin Infect Dis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00971","article-title":"Inside-Out Control of Fc-Receptors","volume":"10","author":"Koenderman","year":"2019","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2011.08.026","article-title":"Infection and Activation of Human Peripheral Blood Monocytes by Dengue Viruses Through the Mechanism of Antibody-Dependent Enhancement","volume":"421","author":"Sun","year":"2011","journal-title":"Virology"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/nri3014","article-title":"Immunity to Dengue Virus: A Tale of Original Antigenic Sin and Tropical Cytokine Storms","volume":"11","author":"Rothman","year":"2011","journal-title":"Nat Rev Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01424-16","article-title":"Characterization of Human CD8 T Cell Responses in Dengue Virus-Infected Patients From India","volume":"90","author":"Chandele","year":"2016","journal-title":"J Virol"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e50387","DOI":"10.1371\/journal.pone.0050387","article-title":"Cellular and Cytokine Correlates of Severe Dengue Infection","volume":"7","author":"Malavige","year":"2012","journal-title":"PloS One"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-017-0625-1","article-title":"Immune-Mediated Cytokine Storm and Its Role in Severe Dengue","volume":"39","author":"Srikiatkhachorn","year":"2017","journal-title":"Semin Immunopathol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"e36435","DOI":"10.1371\/journal.pone.0036435","article-title":"Susceptibility and Response of Human Blood Monocyte Subsets to Primary Dengue Virus Infection","volume":"7","author":"Wong","year":"2012","journal-title":"PloS One"},{"key":"B25","doi-asserted-by":"publisher","first-page":"3897","DOI":"10.1038\/s41467-019-11878-3","article-title":"NK Cells are Activated and Primed for Skin-Homing During Acute Dengue Virus Infection in Humans","volume":"10","author":"Zimmer","year":"2019","journal-title":"Nat Commun"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/j.actatropica.2015.04.023","article-title":"Circulating Cytokines and Chemokines Associated With Plasma Leakage and Hepatic Dysfunction in Brazilian Children With Dengue Fever","volume":"149","author":"Ferreira","year":"2015","journal-title":"Acta Trop"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1993.48.324","article-title":"Serum Levels of Tumor Necrosis Factor-Alpha (TNF-Alpha), Interleukin-6 (IL-6), and Interleukin-1 Beta (IL-1 Beta) in Dengue-Infected Patients","volume":"48","author":"Hober","year":"1993","journal-title":"Am J Trop Med Hyg"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1099\/jgv.0.000637","article-title":"Markers of Dengue Severity: A Systematic Review of Cytokines and Chemokines","volume":"97","author":"Lee","year":"2016","journal-title":"J Gen Virol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"e52215","DOI":"10.1371\/journal.pone.0052215","article-title":"Cytokine Expression Profile of Dengue Patients at Different Phases of Illness","volume":"7","author":"Rathakrishnan","year":"2012","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.05717-11","article-title":"Comparison of Seven Commercial Antigen and Antibody Enzyme-Linked Immunosorbent Assays for Detection of Acute Dengue Infection","volume":"19","author":"Blacksell","year":"2012","journal-title":"Clin Vaccine Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcv.2007.04.003","article-title":"Evaluation of Immunoglobulin M and G Capture Enzyme-Linked Immunosorbent Assay Panbio Kits for Diagnostic Dengue Infections","volume":"39","author":"Vazquez","year":"2007","journal-title":"J Clin Virol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1002\/eji.201970107","article-title":"Guidelines for the Use of Flow Cytometry and Cell Sorting in Immunological Studies (Second Edition)","volume":"49","author":"Cossarizza","year":"2019","journal-title":"Eur J Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1002\/cyto.a.10072","article-title":"Intracellular Phospho-Protein Staining Techniques for Flow Cytometry: Monitoring Single Cell Signaling Events","volume":"55","author":"Krutzik","year":"2003","journal-title":"Cytometry A"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im0624s110","article-title":"Detection of Intracellular Cytokines by Flow Cytometry","volume":"110","author":"Yin","year":"2015","journal-title":"Curr Protoc Immunol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.a.23098","article-title":"Toll-Like Receptor 2bright Cells Identify Circulating Monocytes in Human and Non-Human Primates","volume":"91","author":"Shirk","year":"2017","journal-title":"Cytometry Part A"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1002\/cyto.b.21234","article-title":"Reference Intervals for Leukocyte Subsets in Adults: Results From a Population-Based Study Using 10-Color Flow Cytometry","volume":"88","author":"Melzer","year":"2015","journal-title":"Cytometry Part B: Clin Cytometry"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/j.dib.2017.04.019","article-title":"Reference Values for T, B and NK Human Lymphocyte Subpopulations in Adults","volume":"12","author":"Apoil","year":"2017","journal-title":"Data Brief"},{"key":"B38","doi-asserted-by":"publisher","first-page":"16","DOI":"10.37757\/MR2019.V21.N2-3.5","article-title":"Normal Values of T, B and NK Lymphocyte Subpopulations in Peripheral Blood of Healthy Cuban Adults","volume":"21","author":"Kokuina","year":"2019","journal-title":"MEDICC Rev"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.5772\/62322","article-title":"Analyses of 123 Peripheral Human Immune Cell Subsets: Defining Differences With Age and Between Healthy Donors and Cancer Patients Not Detected in Analysis of Standard Immune Cell Type","volume":"5","author":"Lepone","year":"2016","journal-title":"J Circ Biomark"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1977.26.775","article-title":"Clinical and Laboratory Observations on Patients With Primary and Secondary Dengue Type 1 Infections With Hemorrhagic Manifestations in Fiji","volume":"26","author":"Kuberski","year":"1977","journal-title":"Am J Trop Med Hygiene"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9071(200004)60:4<432::AID-JMV11>3.0.CO;2-7","article-title":"Prospective Study of the Duration and Magnitude of Viraemia in Children Hospitalised During the 1996-1997 Dengue-2 Outbreak in French Polynesia","volume":"60","author":"Murgue","year":"2000","journal-title":"J Med Virol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.06.001","article-title":"Dengue Virus Infection Induces Expansion of a CD14+CD16+ Monocyte Population That Stimulates Plasmablast Differentiation","volume":"16","author":"Kwissa","year":"2014","journal-title":"Cell Host Microbe"},{"key":"B43","doi-asserted-by":"publisher","first-page":"e2298","DOI":"10.1371\/journal.pntd.0002298","article-title":"Sequential Waves of Gene Expression in Patients With Clinically Defined Dengue Illnesses Reveal Subtle Disease Phases and Predict Disease Severity","volume":"7","author":"Sun","year":"2013","journal-title":"PloS Negl Trop Dis"},{"key":"B44","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1186\/s12879-017-2601-8","article-title":"Evaluation of Creatine Kinase and Liver Enzymes in Identification of Severe Dengue","volume":"17","author":"Md Sani","year":"2017","journal-title":"BMC Infect Dis"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1086\/500949","article-title":"Vascular Leakage in Severe Dengue Virus Infections: A Potential Role for the Nonstructural Viral Protein NS1 and Complement","volume":"193","author":"Avirutnan","year":"2006","journal-title":"J Infect Dis"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.1988.38.172","article-title":"A Prospective Study of Dengue Infections in Bangkok","volume":"38","author":"Burke","year":"1988","journal-title":"Am J Trop Med Hygiene"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.aje.a113932","article-title":"Risk Factors in Dengue Shock Syndrome: A Prospective Epidemiologic Study in Rayong, Thailand: I. The 1980 Outbreak","volume":"120","author":"Sangkawibha","year":"1984","journal-title":"Am J Epidemiol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.2006.75.1113","article-title":"Dengue Hemorrhagic Fever Caused by Sequential Dengue 1-3 Virus Infections Over a Long Time Interval: Havana Epidemic, 2001-2002","volume":"75","author":"Alvarez","year":"2006","journal-title":"Am J Trop Med Hyg"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fpubh.2020.00152","article-title":"Gender Differences in Patients With COVID-19: Focus on Severity and Mortality","volume":"8","author":"Jin","year":"2020","journal-title":"Front Public Health"},{"key":"B50","doi-asserted-by":"publisher","first-page":"6317","DOI":"10.1038\/s41467-020-19741-6","article-title":"Male Sex Identified by Global COVID-19 Meta-Analysis as a Risk Factor for Death and ITU Admission","volume":"11","author":"Peckham","year":"2020","journal-title":"Nat Commun"},{"key":"B51","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1186\/1471-2334-13-341","article-title":"Serum IL-10 as a Marker of Severe Dengue Infection","volume":"13","author":"Malavige","year":"2013","journal-title":"BMC Infect Dis"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e2409","DOI":"10.1371\/journal.pntd.0002409","article-title":"Suppression of Virus Specific Immune Responses by IL-10 in Acute Dengue Infection","volume":"7","author":"Malavige","year":"2013","journal-title":"PloS Neglected Trop Dis"},{"key":"B53","doi-asserted-by":"publisher","first-page":"eabd7114","DOI":"10.1126\/sciimmunol.abd7114","article-title":"Comprehensive Mapping of Immune Perturbations Associated With Severe COVID-19","volume":"5","author":"Kuri-Cervantes","year":"2020","journal-title":"Sci Immunol"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.18632\/aging.103582","article-title":"High Neutrophil-to-Lymphocyte Ratio Associated With Progression to Critical Illness in Older Patients With COVID-19: A Multicenter Retrospective Study","volume":"12","author":"Lian","year":"2020","journal-title":"Aging"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e6","DOI":"10.1016\/j.jinf.2020.04.002","article-title":"Neutrophil-To-Lymphocyte Ratio as an Independent Risk Factor for Mortality in Hospitalized Patients With COVID-19","volume":"81","author":"Liu","year":"2020","journal-title":"J Infection"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1097\/SHK.0000000000001585","article-title":"Neutrophil-To-Lymphocyte Ratio and Outcomes in Louisiana COVID-19 Patients","volume":"54","author":"Tatum","year":"2020","journal-title":"Shock"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy053","article-title":"Identification and Characterization at the Single-Cell Level of Cytokine-Producing Circulating Cells in Children With Dengue","volume":"217","author":"Perdomo-Celis","year":"2018","journal-title":"J Infect Dis"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0007892","article-title":"Gene Expression Profiling During Early Acute Febrile Stage of Dengue Infection Can Predict the Disease Outcome","volume":"4","author":"Nascimento","year":"2009","journal-title":"PloS One"},{"key":"B59","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1186\/s12879-016-1596-x","article-title":"Slow Resolution of Inflammation in Severe Adult Dengue Patients","volume":"16","author":"Zhao","year":"2016","journal-title":"BMC Infect Dis"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2588-y","article-title":"Longitudinal Analyses Reveal Immunological Misfiring in Severe COVID-19","volume":"584","author":"Lucas","year":"2020","journal-title":"Nature"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.139834","article-title":"Longitudinal COVID-19 Profiling Associates IL-1RA and IL-10 With Disease Severity and RANTES With Mild Disease","volume":"5","author":"Zhao","year":"2020","journal-title":"JCI Insight"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1086\/520935","article-title":"Elevated Serum Levels of Interferon-\u03b3-Inducible Protein-10 in Patients Coinfected With Hepatitis C Virus and HIV","volume":"196","author":"Roe","year":"2007","journal-title":"J Infect Dis"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1084\/jem.20112142","article-title":"Macrophages Induce Differentiation of Plasma Cells Through CXCL10\/IP-10","volume":"209","author":"Xu","year":"2012","journal-title":"J Exp Med"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1126\/science.abc6027","article-title":"Impaired Type I Interferon Activity and Inflammatory Responses in Severe COVID-19 Patients","volume":"369","author":"Hadjadj","year":"2020","journal-title":"Science"},{"key":"B65","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1016\/j.celrep.2019.01.033","article-title":"A 20-Gene Set Predictive of Progression to Severe Dengue","volume":"26","author":"Robinson","year":"2019","journal-title":"Cell Rep"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12778","article-title":"Expansion of Highly Activated Invariant Natural Killer T Cells With Altered Phenotype in Acute Dengue Infection","volume":"185","author":"Kamaladasa","year":"2016","journal-title":"Clin Exp Immunol"},{"key":"B67","doi-asserted-by":"publisher","first-page":"e2955","DOI":"10.1371\/journal.pntd.0002955","article-title":"Invariant NKT Cell Response to Dengue Virus Infection in Human","volume":"8","author":"Matangkasombut","year":"2014","journal-title":"PloS Neglected Trop Dis"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004607","article-title":"Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever","volume":"10","author":"Cui","year":"2016","journal-title":"PloS Neglected Trop Dis"},{"key":"B69","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3389\/fmicb.2019.02836","article-title":"Quantitative Comparative Proteomics Reveal Biomarkers for Dengue Disease Severity","volume":"10","author":"Han","year":"2019","journal-title":"Front Microbiol"},{"key":"B70","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1186\/s12929-020-0620-z","article-title":"Differential Expression of microRNA, miR-150 and Enhancer of Zeste Homolog 2 (EZH2) in Peripheral Blood Cells as Early Prognostic Markers of Severe Forms of Dengue","volume":"27","author":"Hapugaswatta","year":"2020","journal-title":"J BioMed Sci"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix447","article-title":"Chymase Level Is a Predictive Biomarker of Dengue Hemorrhagic Fever in Pediatric and Adult Patients","volume":"216","author":"Tissera","year":"2017","journal-title":"J Infect Dis"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.677874\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,14]],"date-time":"2021-07-14T09:15:59Z","timestamp":1626254159000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.677874\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,14]]},"references-count":71,"alternative-id":["10.3389\/fimmu.2021.677874"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.677874","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2020.10.14.20212001","asserted-by":"object"}]},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,14]]},"article-number":"677874"}}