{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T19:24:56Z","timestamp":1779909896867,"version":"3.53.1"},"reference-count":57,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T00:00:00Z","timestamp":1634169600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Alpha 7 nicotinic acetylcholine receptor (\u03b17 nAChR) is critical for the pathogenesis of <jats:italic>Escherichia coli<\/jats:italic> (<jats:italic>E. coli<\/jats:italic>) K1 meningitis, a severe central nervous system infection of the neonates. However, little is known about how <jats:italic>E. coli<\/jats:italic> K1 manipulates \u03b17 nAChR signaling. Here, through employing immortalized cell lines, animal models, and human transcriptional analysis, we showed that <jats:italic>E. coli<\/jats:italic> K1 infection triggers releasing of secreted Ly6\/Plaur domain containing 1 (SLURP1), an endogenous \u03b17 nAChR ligand. Exogenous supplement of SLURP1, combined with SLURP1 knockdown or overexpression cell lines, showed that SLURP1 is required for <jats:italic>E. coli<\/jats:italic> K1 invasion and neutrophils migrating across the blood-brain barrier (BBB). Furthermore, we found that SLURP1 is required for <jats:italic>E. coli<\/jats:italic> K1-induced \u03b17 nAChR activation. Finally, the promoting effects of SLURP1 on the pathogenesis of <jats:italic>E. coli<\/jats:italic> K1 meningitis was significantly abolished in the \u03b17 nAChR knockout mice. These results reveal that <jats:italic>E. coli<\/jats:italic> K1 exploits SLURP1 to activate \u03b17 nAChR and facilitate its pathogenesis, and blocking SLURP1-\u03b17 nAChR interaction might represent a novel therapeutic strategy for <jats:italic>E. coli<\/jats:italic> K1 meningitis.<\/jats:p>","DOI":"10.3389\/fimmu.2021.745854","type":"journal-article","created":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T09:22:37Z","timestamp":1634203357000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Endogenous \u03b17 nAChR Agonist SLURP1 Facilitates Escherichia coli K1 Crossing the Blood-Brain Barrier"],"prefix":"10.3389","volume":"12","author":[{"given":"Xiaolong","family":"He","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beiguo","family":"Long","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zelong","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peilin","family":"Zhen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiesong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng-He","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00031","article-title":"Etiology and Clinical Features of Full-Term Neonatal Bacterial Meningitis: A Multicenter Retrospective Cohort Study","volume":"7","author":"Xu","year":"2019","journal-title":"Front Pediatr"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e190874","DOI":"10.1001\/jamanetworkopen.2019.0874","article-title":"Prevalence of Bacteremia and Bacterial Meningitis in Febrile Neonates and Infants in the Second Month of Life: A Systematic Review and Meta-Analysis","volume":"2","author":"Biondi","year":"2019","journal-title":"JAMA Netw Open"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9030535","article-title":"Bacterial Meningitis in Children: Neurological Complications Associated Risk Factors and Prevention","volume":"9","author":"Zainel","year":"2021","journal-title":"Microorganisms"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s13099-019-0290-0","article-title":"Virulence Factors Prevalence and Potential Transmission of Extraintestinal Pathogenic Escherichia Coli Isolated From Different Sources: Recent Reports","volume":"11","author":"Sarowska","year":"2019","journal-title":"Gut Pathog"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e0198772","DOI":"10.1371\/journal.pone.0198772","article-title":"Global Etiology of Bacterial Meningitis: A Systematic Review and Meta-Analysis","volume":"13","author":"Oordt-Speets","year":"2018","journal-title":"PloS One"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy531","article-title":"CD48 and \u03b17 Nicotinic Acetylcholine Receptor Synergistically Regulate fimH-Mediated Escherichia Coli K1 Penetration and Neutrophil Transmigration Across Human Brain Microvascular Endothelial Cells","volume":"219","author":"Liu","year":"2019","journal-title":"J Infect Dis"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.2217\/fmb.11.65","article-title":"Recruitment of \u03b17 Nicotinic Acetylcholine Receptor to Caveolin-1-Enriched Lipid Rafts is Required for Nicotine-Enhanced Escherichia Coli K1 Entry Into Brain Endothelial Cells","volume":"6","author":"Chi","year":"2011","journal-title":"Future Microbiol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"e25016","DOI":"10.1371\/journal.pone.0025016","article-title":"Meningitic Escherichia Coli K1 Penetration and Neutrophil Transmigration Across the Blood\u2013Brain Barrier are Modulated by Alpha7 Nicotinic Receptor","volume":"6","author":"Chi","year":"2011","journal-title":"PloS One"},{"key":"B9","doi-asserted-by":"publisher","first-page":"e0121911","DOI":"10.1371\/journal.pone.0121911","article-title":"Repositioning of Memantine as a Potential Novel Therapeutic Agent Against Meningitic E Coli\u2013induced Pathogenicities Through Disease-Associated Alpha7 Cholinergic Pathway and RNA Sequencing-Based Transcriptome Analysis of Host Inflammatory Responses","volume":"10","author":"Yu","year":"2015","journal-title":"PloS One"},{"key":"B10","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.ijid.2020.09.360","article-title":"Memantine Attenuated E Coli K1-Induced Tight Junction Injuries Through Inhibition of \u03b17 Nachr-Dependent Pathway In Vitro","volume":"101","author":"Qiu","year":"2020","journal-title":"Int J Infect Dis"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2174\/1568007023339283","article-title":"Human Brain Nicotinic Receptors Their Distribution and Participation in Neuropsychiatric Disorders","volume":"1","author":"Graham","year":"2002","journal-title":"Curr Drug Targets CNS Neurol Disord"},{"key":"B12","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1038\/s41568-019-0205-x","article-title":"The Blood\u2013Brain Barrier and Blood\u2013Tumour Barrier in Brain Tumours and Metastases","volume":"20","author":"Arvanitis","year":"2020","journal-title":"Nat Rev Cancer"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e20190062","DOI":"10.1084\/jem.20190062","article-title":"The Blood\u2013Brain Barrier in Health and Disease: Important Unanswered Questions","volume":"217","author":"Profaci","year":"2020","journal-title":"J Exp Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"352","DOI":"10.1186\/s12879-015-1075-9","article-title":"Alpha7 Nicotinic Acetylcholine Receptor Is Required for Blood-Brain Barrier Injury-Related CNS Disorders Caused by Cryptococcus Neoformans and HIV-1 Associated Comorbidity Factors","volume":"15","author":"Zhang","year":"2015","journal-title":"BMC Infect Dis"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1046\/j.1462-5822.2002.00209.x","article-title":"Enhanced Escherichia Coli Invasion of Human Brain Microvascular Endothelial Cells is Associated With Alterations in Cytoskeleton Induced by Nicotine","volume":"4","author":"Chen","year":"2002","journal-title":"Cell Microbiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2020.00513","article-title":"Effects of Drugs of Abuse on the Blood-Brain Barrier: A Brief Overview","volume":"14","author":"Pimentel","year":"2020","journal-title":"Front Neurosci"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X15616978","article-title":"Drugs of Abuse and Blood-Brain Barrier Endothelial Dysfunction: A Focus on the Role of Oxidative Stress","volume":"36","author":"Sajja","year":"2016","journal-title":"J Cereb Blood Flow Metab"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2020.00484","article-title":"Nicotine Reduces Human Brain Microvascular Endothelial Cell Response to Escherichia Coli K1 Infection by Inhibiting Autophagy","volume":"10","author":"Wu","year":"2012","journal-title":"Front Cell Infect Microbiol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2458-12-1062","article-title":"Second Hand Smoke Exposure and the Risk of Invasive Meningococcal Disease in Children: Systematic Review and Meta-Analysis","volume":"12","author":"Murray","year":"2012","journal-title":"BMC Public Health"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1186\/1617-9625-4-12","article-title":"Tobacco Use Increases Susceptibility to Bacterial Infection","volume":"4","author":"Bagaitkar","year":"2008","journal-title":"Tob Induc Dis"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2013.07.048","article-title":"Effect of Secreted Lymphocyte Antigen-6\/Urokinase-Type Plasminogen Activator Receptor-Related Peptide-1 (SLURP-1) on Airway Epithelial Cells","volume":"438","author":"Narumoto","year":"2013","journal-title":"Biochem Biophys Res Commun"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddg320","article-title":"Identification of SLURP-1 as an Epidermal Neuromodulator Explains the Clinical Phenotype of Mal De Meleda","volume":"12","author":"Chimienti","year":"2003","journal-title":"Hum Mol Genet"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1110\/ps.8.4.810","article-title":"Structural and Phylogenetic Characterization of Human SLURP-1, the First Secreted Mammalian Member of the Ly-6\/uPAR Protein Superfamily","volume":"8","author":"Adermann","year":"1999","journal-title":"Protein Sci"},{"key":"B24","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1016\/s0165-5728(97)00036-2","article-title":"Selective Expression of Adhesion Molecules on Human Brain Microvascular Endothelial Cells","volume":"76","author":"Stins","year":"1997","journal-title":"J Neuroimmunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1186\/s12929-016-0247-2","article-title":"CD44-Mediated Monocyte Transmigration Across Cryptococcus Neoformans-Infected Brain Microvascular Endothelial Cells is Enhanced by HIV-1 Gp41-I90 Ectodomain","volume":"23","author":"He","year":"2016","journal-title":"J BioMed Sci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pharmthera.2017.05.002","article-title":"Cholinergic Modulation of the Immune System Presents New Approaches for Treating Inflammation","volume":"179","author":"Hoover","year":"2017","journal-title":"Pharmacol Therapeut"},{"key":"B27","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.redox.2017.11.013","article-title":"Cholinergic Anti-Inflammatory Pathway Inhibits Neointimal Hyperplasia by Suppressing Inflammation and Oxidative Stress","volume":"15","author":"Li","year":"2018","journal-title":"Redox Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s10020-020-00184-0","article-title":"The Cholinergic Anti-Inflammatory Pathway Alleviates Acute Lung Injury","volume":"26","author":"Andersson","year":"2020","journal-title":"Mol Med"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s40520-019-01359-4","article-title":"Acetylcholinesterase Inhibitors Targeting the Cholinergic Anti-Inflammatory Pathway: A New Therapeutic Perspective in Aging-Related Disorders","volume":"33","author":"Benfante","year":"2021","journal-title":"Aging Clin Exp Res"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s11154-020-09584-3","article-title":"Therapeutic Potential of \u03b17 Nicotinic Acetylcholine Receptor Agonists to Combat Obesity Diabetes and Inflammation","volume":"21","author":"Xie","year":"2020","journal-title":"Rev Endocr Metab Disord"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1183\/09031936.00103408","article-title":"Stimulation of Acetylcholine Receptors Impairs Host Defence During Pneumococcal Pneumonia","volume":"33","author":"Giebelen","year":"2009","journal-title":"Eur Respir J"},{"key":"B32","doi-asserted-by":"publisher","first-page":"e0116861","DOI":"10.1371\/journal.pone.0116861","article-title":"Exposure to Electronic Cigarettes Impairs Pulmonary Anti-Bacterial and Anti-Viral Defenses in a Mouse Model","volume":"10","author":"Sussan","year":"2015","journal-title":"PloS One"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0901808","article-title":"Requisite Role of the Cholinergic \u03b17 Nicotinic Acetylcholine Receptor Pathway in Suppressing Gram-Negative Sepsis-Induced Acute Lung Inflammatory Injury","volume":"184","author":"Su","year":"2010","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.03.009","article-title":"Neuroendocrine Nicotinic Receptor Activation Increases Susceptibility to Bacterial Infections by Suppressing Antimicrobial Peptide Production","volume":"7","author":"Radek","year":"2010","journal-title":"Cell Host Microbe"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.phrs.2016.12.014","article-title":"Therapeutic Potential and Limitations of Cholinergic Anti-Inflammatory Pathway in Sepsis","volume":"117","author":"Kanashiro","year":"2017","journal-title":"Pharmacol Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.11.6518","article-title":"Involvement of Nicotinic Acetylcholine Receptors in Suppression of Antimicrobial Activity and Cytokine Responses of Alveolar Macrophages to Legionella Pneumophila Infection by Nicotine","volume":"167","author":"Matsunaga","year":"2001","journal-title":"J Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1086\/590432","article-title":"Deficiency of Alpha7 Cholinergic Receptors Facilitates Bacterial Clearance in Escherichia Coli Peritonitis","volume":"198","author":"Giebelen","year":"2008","journal-title":"J Infect Dis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.15123","article-title":"Three-Finger Proteins From Snakes and Humans Acting on Nicotinic Receptors: Old and New","volume":"158","author":"Tsetlin","year":"2020","journal-title":"J Neurochem"},{"key":"B39","first-page":"3325","article-title":"Secreted Ly-6\/uPAR Related Protein-1 (SLURP1) Modulates Inflammation by Influencing Both Neutrophils and Endothelial Cells","volume":"59","author":"Swamynathan","year":"2018","journal-title":"Invest Ophth Vis Sci"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.07.123","article-title":"The Secreted Ly-6\/uPAR Related Protein-1 (SLURP1) Stabilizes Epithelial Cell Junctions and Suppresses TNF-\u03b1-Induced Cytokine Production","volume":"517","author":"Campbell","year":"2019","journal-title":"Biochem Biophys Res Commun"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.631881","article-title":"New Pathways for the Skin's Stress Response: The Cholinergic Neuropeptide SLURP-1 Can Activate Mast Cells and Alter Cytokine Production in Mice","volume":"12","author":"Ertle","year":"2021","journal-title":"Front Immunol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"5898","DOI":"10.1038\/s41598-019-42437-x","article-title":"The Secreted Ly6\/uPAR-Related Protein-1 Suppresses Neutrophil Binding Chemotaxis and Transmigration Through Human Umbilical Vein Endothelial Cells","volume":"9","author":"Swamynathan","year":"2019","journal-title":"Sci Rep"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/609086","article-title":"Anti-Inflammatory Effects of the Nicotinergic Peptides SLURP-1 and SLURP-2 on Human Intestinal Epithelial Cells and Immunocytes","volume":"2014","author":"Chernyavsky","year":"2014","journal-title":"BioMed Res Int"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01085","article-title":"Expression and Function of the Cholinergic System in Immune Cells","volume":"8","author":"Fujii","year":"2017","journal-title":"Front Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2009.04.014","article-title":"Primary Sensory Neuronal Expression of SLURP-1 an Endogenous Nicotinic Acetylcholine Receptor Ligand","volume":"64","author":"Moriwaki","year":"2009","journal-title":"Neurosci Res"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1134\/S0006297917130090","article-title":"Three-Finger Proteins From the Ly6\/uPAR Family: Functional Diversity Within One Structural Motif","volume":"82","author":"Vasilyeva","year":"2017","journal-title":"Biochem (Moscow)"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.12-10759","article-title":"Klf4 Regulates the Expression of Slurp1 Which Functions as an Immunomodulatory Peptide in the Mouse Cornea","volume":"53","author":"Swamynathan","year":"2012","journal-title":"Invest Ophth Vis Sci"},{"key":"B48","first-page":"4298","article-title":"Slurp-1 Promoter Activity Is Regulated by KLF4 in the Corneal Epithelial and Skin Keratinocytes","volume":"49","author":"Swamynathan","year":"2008","journal-title":"Invest Ophth Vis Sci"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2020.582070","article-title":"Induction of Krueppel-Like Factor 4 Mediates Polymorphonuclear Neutrophil Activation in Streptococcus Pneumoniae Infection","volume":"11","author":"Bhattacharyya","year":"2020","journal-title":"Front Microbiol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances","article-title":"Kruppel-Like Factor 4 Regulates Neutrophil Activation","volume":"1","author":"Shen","year":"2017","journal-title":"Blood Adv"},{"key":"B51","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1042\/BJ20091097","article-title":"Vimentin-Mediated Signalling is Required for IbeA+ E Coli K1 Invasion of Human Brain Microvascular Endothelial Cells","volume":"427","author":"Chi","year":"2010","journal-title":"Biochem J"},{"key":"B52","doi-asserted-by":"publisher","first-page":"e0162641","DOI":"10.1371\/journal.pone.0162641","article-title":"Vimentin, a Novel NF-\u03bab Regulator is Required for Meningitic Escherichia Coli K1-Induced Pathogen Invasion and PMN Transmigration Across the Blood-Brain Barrier","volume":"11","author":"Huang","year":"2016","journal-title":"PloS One"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00216.2010","article-title":"Upregulation of Nuclear Factor-\u03bab Expression by SLURP-1 is Mediated by \u03b17-Nicotinic Acetylcholine Receptor and Involves Both Ionic Events and Activation of Protein Kinases","volume":"299","author":"Chernyavsky","year":"2010","journal-title":"Am J Physiol Cell Physiol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"e62164","DOI":"10.1371\/journal.pone.0062164","article-title":"Circulating Brain Microvascular Endothelial Cells (cBMECs) as Potential Biomarkers of the Blood-Brain Barrier Disorders Caused by Microbial and non-Microbial Factors","volume":"8","author":"Huang","year":"2013","journal-title":"PloS One"},{"key":"B55","doi-asserted-by":"publisher","first-page":"16606","DOI":"10.1038\/s41598-017-16809-0","article-title":"Interaction of Synthetic Human SLURP-1 With the Nicotinic Acetylcholine Receptors","volume":"7","author":"Durek","year":"2017","journal-title":"Sci Rep"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jid.5700551","article-title":"SLURP1 is a Late Marker of Epidermal Differentiation and is Absent in Mal De Meleda","volume":"127","author":"Favre","year":"2007","journal-title":"J Invest Dermatol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200206096","article-title":"Central Role of Alpha7 Nicotinic Receptor in Differentiation of the Stratified Squamous Epithelium","volume":"159","author":"Arredondo","year":"2002","journal-title":"J Cell Biol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.745854\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T09:22:41Z","timestamp":1634203361000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.745854\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,14]]},"references-count":57,"alternative-id":["10.3389\/fimmu.2021.745854"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.745854","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,14]]},"article-number":"745854"}}