{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:49:32Z","timestamp":1793659772257,"version":"4.5.1"},"reference-count":59,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T00:00:00Z","timestamp":1636934400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST109-2320-B-038-050, 109-2327-B-006-010, and 110-2320-B-038 -064 -MY3"],"award-info":[{"award-number":["MOST109-2320-B-038-050, 109-2327-B-006-010, and 110-2320-B-038 -064 -MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Infection with flaviviruses causes mild to severe diseases, including viral hemorrhagic fever, vascular shock syndrome, and viral encephalitis. Several animal models explore the pathogenesis of viral encephalitis, as shown by neuron destruction due to neurotoxicity after viral infection. While neuronal cells are injuries caused by inflammatory cytokine production following microglial\/macrophage activation, the blockade of inflammatory cytokines can reduce neurotoxicity to improve the survival rate. This study investigated the involvement of macrophage phenotypes in facilitating CNS inflammation and neurotoxicity during flavivirus infection, including the Japanese encephalitis virus, dengue virus (DENV), and Zika virus. Mice infected with different flaviviruses presented encephalitis-like symptoms, including limbic seizure and paralysis. Histology indicated that brain lesions were identified in the hippocampus and surrounded by mononuclear cells. In those regions, both the infiltrated macrophages and resident microglia were significantly increased. RNA-seq analysis showed the gene profile shifting toward type 1 macrophage (M1) polarization, while M1 markers validated this phenomenon. Pharmacologically blocking C-C chemokine receptor 2 and tumor necrosis factor-\u03b1 partly retarded DENV-induced M1 polarization. In summary, flavivirus infection, such as JEV and DENV, promoted type 1 macrophage polarization in the brain associated with encephalitic severity.<\/jats:p>","DOI":"10.3390\/cells10113181","type":"journal-article","created":{"date-parts":[[2021,11,15]],"date-time":"2021-11-15T20:46:47Z","timestamp":1637009207000},"page":"3181","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Polarization of Type 1 Macrophages Is Associated with the Severity of Viral Encephalitis Caused by Japanese Encephalitis Virus and Dengue Virus"],"prefix":"10.3390","volume":"10","author":[{"given":"Ming-Kai","family":"Jhan","sequence":"first","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1714-0048","authenticated-orcid":false,"given":"Ting-Jing","family":"Shen","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Po-Chun","family":"Tseng","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Core Laboratory of Immune Monitoring, Office of Research & Development, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yung-Ting","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahmat Dani","family":"Satria","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Laboratory Medicine, Department of Clinical Pathology, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta 55281, Indonesia"},{"name":"Clinical Laboratory Installation, Dr. Sardjito Central General Hospital, Yogyakarta 55281, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Yi","family":"Yu","sequence":"additional","affiliation":[{"name":"National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Miaoli 350, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4396-6086","authenticated-orcid":false,"given":"Chiou-Feng","family":"Lin","sequence":"additional","affiliation":[{"name":"Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Department of Microbiology and Immunology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"},{"name":"Core Laboratory of Immune Monitoring, Office of Research & Development, Taipei Medical University, Taipei 110, Taiwan"},{"name":"International Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/s41564-020-0714-0","article-title":"The continued threat of emerging flaviviruses","volume":"5","author":"Pierson","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1517\/14712598.2012.704908","article-title":"Clinical development of IMOJEV \u00ae\u2014A recombinant Japanese encephalitis chimeric vaccine (JE-CV)","volume":"12","author":"Appaiahgari","year":"2012","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"8905","DOI":"10.1128\/JVI.00937-07","article-title":"The C terminus of hepatitis C virus NS4A encodes an electrostatic switch that regulates NS5A hyperphosphorylation and viral replication","volume":"81","author":"Lindenbach","year":"2007","journal-title":"J. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1128\/JVI.80.5.2170-2182.2006","article-title":"RNA secondary structure in the coding region of dengue virus type 2 directs translation start codon selection and is required for viral replication","volume":"80","author":"Clyde","year":"2006","journal-title":"J. Virol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1128\/CMR.13.1.67","article-title":"Perspectives for the treatment of infections with Flaviviridae","volume":"13","author":"Leyssen","year":"2000","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1016\/S0140-6736(08)60238-X","article-title":"Pathogenic flaviviruses","volume":"371","author":"Gould","year":"2008","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1136\/jnnp.68.4.405","article-title":"Japanese encephalitis","volume":"68","author":"Solomon","year":"2000","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1038\/ncpneuro0176","article-title":"West Nile virus meningoencephalitis","volume":"2","author":"Debiasi","year":"2006","journal-title":"Nat. Clin. Pract. Neurol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"430","DOI":"10.12998\/wjcc.v3.i5.430","article-title":"Tick-borne encephalitis: A review of epidemiology, clinical characteristics, and management","volume":"3","author":"Bogovic","year":"2015","journal-title":"World J. Clin. Cases"},{"key":"ref_10","unstructured":"(2009). WHO Guidelines Approved by the Guidelines Review Committee. Dengue: Guidelines for Diagnosis, Treatment, Prevention and Control: New Edition, World Health Organization."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1007\/s13365-012-0117-y","article-title":"In vivo infection by a neuroinvasive neurovirulent dengue virus","volume":"18","author":"Castellanos","year":"2012","journal-title":"J. Neurovirol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27670","DOI":"10.1038\/srep27670","article-title":"Microglia retard dengue virus-induced acute viral encephalitis","volume":"6","author":"Tsai","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_13","first-page":"E42","article-title":"Dengue hemorrhage in a mouse model","volume":"1171","author":"Yen","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.bbr.2012.02.020","article-title":"Dengue-3 encephalitis promotes anxiety-like behavior in mice","volume":"230","author":"Rodrigues","year":"2012","journal-title":"Behav. Brain Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1038\/s41598-017-00182-z","article-title":"Dengue virus infection increases microglial cell migration","volume":"7","author":"Jhan","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/j.imbio.2015.06.002","article-title":"Novel evidence of microglial immune response in impairment of Dengue infection of CNS","volume":"220","author":"Bhatt","year":"2015","journal-title":"Immunobiology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1002\/JLB.MA1217-484R","article-title":"Anti-TNF-\u03b1 restricts dengue virus-induced neuropathy","volume":"104","author":"Jhan","year":"2018","journal-title":"J. Leukoc. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e00525-18","DOI":"10.1128\/JVI.00525-18","article-title":"Pharmacologic Depletion of Microglia Increases Viral Load in the Brain and Enhances Mortality in Murine Models of Flavivirus-Induced Encephalitis","volume":"92","author":"Seitz","year":"2018","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1017\/S1740925X12000063","article-title":"Functions of microglia in the central nervous system\u2014Beyond the immune response","volume":"7","author":"Wake","year":"2011","journal-title":"Neuron Glia Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/B978-0-444-63432-0.00003-7","article-title":"The blood-brain barrier","volume":"133","author":"Obermeier","year":"2016","journal-title":"Handb. Clin. Neurol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"a020545","DOI":"10.1101\/cshperspect.a020545","article-title":"Microglia Function in Central Nervous System Development and Plasticity","volume":"7","author":"Schafer","year":"2015","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.3390\/ph7121028","article-title":"Role of microglial m1\/m2 polarization in relapse and remission of psychiatric disorders and diseases","volume":"7","author":"Nakagawa","year":"2014","journal-title":"Pharmaceuticals"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nrneurol.2014.207","article-title":"Microglial and macrophage polarization\u2014New prospects for brain repair","volume":"11","author":"Hu","year":"2015","journal-title":"Nat. Rev. Neurol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"77","DOI":"10.3389\/fnana.2017.00077","article-title":"Microglia Polarization with M1\/M2 Phenotype Changes in rd1 Mouse Model of Retinal Degeneration","volume":"11","author":"Zhou","year":"2017","journal-title":"Front. Neuroanat."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/1742-2094-11-98","article-title":"Neuroinflammation and M2 microglia: The good, the bad, and the inflamed","volume":"11","author":"Cherry","year":"2014","journal-title":"J. Neuroinflamm."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"5602","DOI":"10.1128\/JVI.00143-15","article-title":"Viral Infection of the Central Nervous System and Neuroinflammation Precede Blood-Brain Barrier Disruption during Japanese Encephalitis Virus Infection","volume":"89","author":"Li","year":"2015","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"525","DOI":"10.3389\/fmicb.2019.00525","article-title":"Pathways Exploited by Flaviviruses to Counteract the Blood-Brain Barrier and Invade the Central Nervous System","volume":"10","author":"Meuren","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1038\/s41564-017-0060-z","article-title":"Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice","volume":"3","author":"Jurado","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.3389\/fimmu.2018.01148","article-title":"IP-10 Promotes Blood-Brain Barrier Damage by Inducing Tumor Necrosis Factor Alpha Production in Japanese Encephalitis","volume":"9","author":"Wang","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1016\/j.virol.2009.10.036","article-title":"Reversal of West Nile virus-induced blood-brain barrier disruption and tight junction proteins degradation by matrix metalloproteinases inhibitor","volume":"397","author":"Verma","year":"2010","journal-title":"Virology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"557610","DOI":"10.3389\/fcimb.2020.557610","article-title":"CNS Immune Profiling in a Dengue Virus-Infected Immunocompetent Outbred ICR Mice Strain","volume":"10","author":"Shen","year":"2020","journal-title":"Front. Cell Infect. Microbiol."},{"key":"ref_32","first-page":"146","article-title":"A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease","volume":"28","author":"Shen","year":"2019","journal-title":"J. Vis. Exp."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.3389\/fimmu.2019.01084","article-title":"Macrophage Polarization: Different Gene Signatures in M1(LPS+) vs. Classically and M2(LPS\u2013) vs. Alternatively Activated Macrophages","volume":"10","author":"Orecchioni","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"230","DOI":"10.3389\/fncel.2020.00230","article-title":"CCR2 Inhibition Reduces Neurotoxic Microglia Activation Phenotype After Japanese Encephalitis Viral Infection","volume":"14","author":"Singh","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1186\/s12974-017-1015-2","article-title":"Neuronal CCL2 expression drives inflammatory monocyte infiltration into the brain during acute virus infection","volume":"14","author":"Howe","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"215","DOI":"10.3389\/fncel.2018.00215","article-title":"Microglia Responses to Pro-inflammatory Stimuli (LPS, IFN\u03b3+TNF\u03b1) and Reprogramming by Resolving Cytokines (IL-4, IL-10)","volume":"12","author":"Lively","year":"2018","journal-title":"Front. Cell. Neurosci."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2222","DOI":"10.4049\/jimmunol.1900003","article-title":"miR-301a Regulates Inflammatory Response to Japanese Encephalitis Virus Infection via Suppression of NKRF Activity","volume":"203","author":"Hazra","year":"2019","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"651","DOI":"10.3389\/fmicb.2017.00651","article-title":"Japanese Encephalitis Virus Exploits Dopamine D2 Receptor-phospholipase C to Target Dopaminergic Human Neuronal Cells","volume":"8","author":"Simanjuntak","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3890","DOI":"10.1038\/s41467-019-11866-7","article-title":"Zika virus replicates in adult human brain tissue and impairs synapses and memory in mice","volume":"10","author":"Figueiredo","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Potokar, M., Jorga\u010devski, J., and Zorec, R. (2019). Astrocytes in Flavivirus Infections. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20030691"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/BF00688063","article-title":"Characteristic residual neuropathological features of Japanese B encephalitis","volume":"38","author":"Ishii","year":"1977","journal-title":"Acta Neuropathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"9844","DOI":"10.1128\/JVI.72.12.9844-9854.1998","article-title":"Antiapoptotic but not antiviral function of human bcl-2 assists establishment of Japanese encephalitis virus persistence in cultured cells","volume":"72","author":"Liao","year":"1998","journal-title":"J. Virol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"5963","DOI":"10.1128\/jvi.71.8.5963-5971.1997","article-title":"Effect of enforced expression of human bcl-2 on Japanese encephalitis virus-induced apoptosis in cultured cells","volume":"71","author":"Liao","year":"1997","journal-title":"J. Virol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1128\/iai.8.6.1017-1028.1973","article-title":"Dengue virus infection of mice: Morphology and morphogenesis of dengue type-2 virus in suckling mouse neurones","volume":"8","author":"Sriurairatna","year":"1973","journal-title":"Infect. Immun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3389\/fcimb.2020.00489","article-title":"Inflammasome Fuels Dengue Severity","volume":"10","author":"Shrivastava","year":"2020","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1590\/S0074-02762009000800005","article-title":"Dengue-2 infection and the induction of apoptosis in human primary monocytes","volume":"104","author":"Azeredo","year":"2009","journal-title":"Mem\u00f3rias Do Inst. Oswaldo Cruz"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1038\/nri.2016.153","article-title":"Programmed cell death and the immune system","volume":"17","author":"Nagata","year":"2017","journal-title":"Nat. Rev. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e00602-20","DOI":"10.1128\/JVI.00602-20","article-title":"Axl Deficiency Promotes the Neuroinvasion of Japanese Encephalitis Virus by Enhancing IL-1\u03b1 Production from Pyroptotic Macrophages","volume":"94","author":"Wang","year":"2020","journal-title":"J. Virol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"3240","DOI":"10.1172\/JCI90606","article-title":"Microglia in Alzheimer\u2019s disease","volume":"127","author":"Sarlus","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1007\/s12035-014-9070-5","article-title":"Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases","volume":"53","author":"Tang","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1146\/annurev-immunol-042718-041417","article-title":"Neuroinflammation During RNA Viral Infections","volume":"37","author":"Klein","year":"2019","journal-title":"Annu. Rev. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1161\/01.STR.32.5.1208","article-title":"Enhanced expression of Iba1, ionized calcium-binding adapter molecule 1, after transient focal cerebral ischemia in rat brain","volume":"32","author":"Ito","year":"2001","journal-title":"Stroke"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"8825954","DOI":"10.1155\/2020\/8825954","article-title":"Inhibited CSF1R Alleviates Ischemia Injury via Inhibition of Microglia M1 Polarization and NLRP3 Pathway","volume":"2020","author":"Du","year":"2020","journal-title":"Neural Plast."},{"key":"ref_54","first-page":"2006","article-title":"Modulators of microglia activation and polarization in ischemic stroke (Review)","volume":"21","author":"Jiang","year":"2020","journal-title":"Mol. Med. Rep."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"948098","DOI":"10.1155\/2012\/948098","article-title":"Macrophages in Tumor Microenvironments and the Progression of Tumors","volume":"2012","author":"Hao","year":"2012","journal-title":"Clin. Dev. Immunol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"583084","DOI":"10.3389\/fimmu.2020.583084","article-title":"Tumor-Associated Macrophages in Tumor Immunity","volume":"11","author":"Pan","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"6425","DOI":"10.1002\/jcp.26429","article-title":"Macrophage plasticity, polarization, and function in health and disease","volume":"233","author":"Mohammadian","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.4049\/jimmunol.1701135","article-title":"M1 Means Kill; M2 Means Heal","volume":"199","author":"Ley","year":"2017","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1093\/infdis\/jiu179","article-title":"Etanercept Reduces Neuroinflammation and Lethality in Mouse Model of Japanese Encephalitis","volume":"210","author":"Ye","year":"2014","journal-title":"J. Infect. Dis."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3181\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:30:42Z","timestamp":1760167842000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/10\/11\/3181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,15]]},"references-count":59,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,11]]}},"alternative-id":["cells10113181"],"URL":"https:\/\/doi.org\/10.3390\/cells10113181","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,15]]}}}