{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:54:03Z","timestamp":1776315243071,"version":"3.50.1"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T00:00:00Z","timestamp":1776297600000},"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:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      IbeA is a critical virulence factor that is present in the GimA island in\n                      <jats:italic>Escherichia coli<\/jats:italic>\n                      (\n                      <jats:italic>E. coli<\/jats:italic>\n                      ) K1, the most common cause of Gram-negative bacterial meningitis in newborns. IbeA has multiple virulence functions, including adhesion, invasion, and biofilm formation in the pathogenesis of\n                      <jats:italic>E. coli<\/jats:italic>\n                      K1 meningitis. However, it is unclear how IbeA coordinates its role in bacterial adhesion, invasion, and biofilm formation during crossing the blood-brain barrier (BBB).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      An isogenic\n                      <jats:italic>ibeA<\/jats:italic>\n                      deletion mutant (ZD1) was generated from the neonatal meningitis\u2013associated\n                      <jats:italic>E. coli<\/jats:italic>\n                      K1 strain E44. To define IbeA-mediated virulence, bacterial adhesion, invasion, and biofilm formation were quantified in human brain microvascular endothelial cells (HBMECs) using TEER, confocal imaging, and crystal violet assays. A neonatal rat meningitis model evaluated bacterial dissemination, BBB disruption, neuroinflammation, and neurological deficits. Mechanistic studies focused on Vimentin (VIM) dynamics using lipid-raft fractionation, cytoskeleton extraction, immunofluorescence, vimentin-knockout (Vim-KO) HBMEC and Co-immunoprecipitation to assess its redistribution, post-translational modifications, and interaction with NF-\u03baB. The functional involvement of the IbeA\u2013VIM\u2013NF-\u03baB signaling pathway was further examined by modulating VIM activity with glatiramer acetate (GA) in both\n                      <jats:italic>in vitro<\/jats:italic>\n                      and\n                      <jats:italic>in vivo<\/jats:italic>\n                      experiments.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Deletion of\n                      <jats:italic>ibeA<\/jats:italic>\n                      and VIM significantly impaired bacterial adhesion, invasion, and biofilm formation both on HBMECs and on abiotic surfaces. In neonatal rats, infection with ZD1 resulted in higher survival rates, milder neurological symptoms, and a marked reduction of biofilm structures within the cerebral microvasculature compared with infection by the wild-type strain. IbeA-triggered post-translational modifications and cytoplasmic mobilization of VIM drive its nuclear translocation, which in turn activates NF-\u03baB signaling. Pharmacological inhibition of VIM with GA disrupted IbeA-mediated virulence, lowering bacterial loads in the blood and alleviating neurological injury.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      IbeA is a key virulence factor that coordinates\n                      <jats:italic>E. coli<\/jats:italic>\n                      K1 adhesion, invasion, and biofilm formation by activating the VIM\u2013NF-\u03baB signaling pathway. Our study establishes for the first time a direct mechanistic link between IbeA\u2019s multiple virulence functions through the above signaling pathway leading to acute BBB disruption and meningitis and identify GA as a potential drug development candidate for this disease.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1793594","type":"journal-article","created":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:20:31Z","timestamp":1776313231000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Vimentin\u2013NF-\u03baB signaling contributing to IbeA-mediated adhesion, invasion, and biofilm formation during Escherichia coli K1 traversal of the blood\u2013brain barrier"],"prefix":"10.3389","volume":"17","author":[{"given":"Bingliang","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangshun","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhengying","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biological Safety Laboratory of Level 3 (BSL-3) Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Zhao","sequence":"additional","affiliation":[{"name":"Biological Safety Laboratory of Level 3 (BSL-3) Laboratory (Guangdong), Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Wang","sequence":"additional","affiliation":[{"name":"Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, Southern Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, The Fifth Affiliated Hospital of Guangzhou Medical University","place":["Guangzhou, Guangdong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinhu","family":"Zou","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuefeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng-He","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]},{"name":"Department of Pediatrics, University of Southern California","place":["Los Angeles, CA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University","place":["Guangzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1186\/s12879-015-1210-7","article-title":"The molecular characterization of Escherichia coli k1 isolated from neonatal nasogastric feeding tubes","volume":"15","author":"Alkeskas","year":"2015","journal-title":"BMC Infect Dis"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms241310580","article-title":"Phage targeting neonatal meningitis E. coli K1 in vitro in the intestinal microbiota of pregnant donors and impact on bacterial populations","volume":"24","author":"Antoine","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00125-13","article-title":"Escherichia coli ST131, an intriguing clonal group","volume":"27","author":"Nicolas-Chanoine","year":"2014","journal-title":"Clin Microbiol Rev"},{"key":"B4","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12887-023-03866-w","article-title":"The genotypic and phenotypic characteristics contributing to high virulence and antibiotics resistance in Escherichia coli O25-B2-ST131 in comparison to non- O25-B2-ST131","volume":"23","author":"Shahbazi","year":"2023","journal-title":"BMC Pediatr"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-015-6925-2","article-title":"The effects of upaB deletion and the double\/triple deletion of upaB, aatA, and aatB genes on pathogenicity of avian pathogenic Escherichia coli","volume":"99","author":"Zhu-Ge","year":"2015","journal-title":"Appl Microbiol Biotechnol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.06388-11","article-title":"Virulence of Escherichia coli clinical isolates in a murine sepsis model in relation to sequence type ST131 status, fluoroquinolone resistance, and virulence genotype","volume":"80","author":"Johnson","year":"2012","journal-title":"Infect Immun"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1128\/AEM.01112-10","article-title":"Recent emergence of clonal group O25b: K1:H4-B2-ST131 ibeA strains among Escherichia coli poultry isolates, including CTX-m-9-producing strains, and comparison with clinical human isolates","volume":"76","author":"Mora","year":"2010","journal-title":"Appl Environ Microbiol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1007\/s101420100039","article-title":"A novel genetic island of meningitic Escherichia coli k1 containing the ibeA invasion gene (GimA): functional annotation and carbon-source-regulated invasion of human brain microvascular endothelial cells","volume":"1","author":"Huang","year":"2001","journal-title":"Funct Integr Genomics"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1086\/319290","article-title":"Further characterization of Escherichia coli brain microvascular endothelial cell invasion gene ibea by deletion, complementation, and protein expression","volume":"183","author":"Huang","year":"2001","journal-title":"J Infect Dis"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1111\/lam.12349","article-title":"Distribution of virulence genes and multiple drug-resistant patterns amongst different phylogenetic groups of uropathogenic Escherichia coli isolated from patients with urinary tract infection","volume":"60","author":"Derakhshandeh","year":"2015","journal-title":"Lett Appl Microbiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/JB.00089-12","article-title":"New role for the ibeA gene in h2o2 stress resistance of Escherichia coli","volume":"194","author":"Fl\u00e9chard","year":"2012","journal-title":"J Bacteriol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1099\/mic.0.27809-0","article-title":"IbeA, a virulence factor of avian pathogenic Escherichia coli","volume":"151","author":"Germon","year":"2005","journal-title":"Microbiol (Reading)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00821-10","article-title":"Effects of Iber deletion on virulence and biofilm formation of avian pathogenic Escherichia coli","volume":"79","author":"Wang","year":"2011","journal-title":"Infect Immun"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2025.123886","article-title":"The silent invaders: biofilms in neurological, cardiovascular, and metabolic diseases","volume":"379","author":"Kumar","year":"2025","journal-title":"Life Sci"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1093\/jambio\/lxae109","article-title":"K1 capsule-dependent phage-driven evolution in Escherichia coli leading to phage resistance and biofilm production","volume":"135","author":"Antoine","year":"2024","journal-title":"J Appl Microbiol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24032852","article-title":"Blood-brain barrier integrity damage in bacterial meningitis: the underlying link, mechanisms, and therapeutic targets","volume":"24","author":"Yang","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B17","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1042\/BJ20091097","article-title":"Vimentin-mediated signaling 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":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.10.091","article-title":"Identification of a surface protein on human brain microvascular endothelial cells as vimentin interacting with Escherichia coli invasion protein IbeA","volume":"351","author":"Zou","year":"2006","journal-title":"Biochem Biophys Res Commun"},{"key":"B19","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1111\/j.1750-3639.2010.00463.x","article-title":"Involvement of IbeA in meningitic Escherichia coli K1-induced polymorphonuclear leukocyte transmigration across brain endothelial cells","volume":"21","author":"Che","year":"2011","journal-title":"Brain Pathol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0035862","article-title":"Vimentin and PSF act in concert to regulate IbeA+ e. Coli k1 induced activation and nuclear translocation of NF-\u03baB in human brain endothelial cells","volume":"7","author":"Chi","year":"2012","journal-title":"PloS One"},{"key":"B21","doi-asserted-by":"publisher","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":"B22","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/7592851","article-title":"An overview of the intrinsic role of citrullination in autoimmune disorders","volume":"2019","author":"Alghamdi","year":"2019","journal-title":"J Immunol Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1128\/genomeA.00804-15","article-title":"Complete genome sequence of Escherichia coli strain RS218 (O18:H7: K1), associated with neonatal meningitis","volume":"3","author":"Wijetunge","year":"2015","journal-title":"Genome Announc"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro1952","article-title":"Mechanisms of microbial traversal of the blood-brain barrier","volume":"6","author":"Kim","year":"2008","journal-title":"Nat Rev Microbiol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/2045-8118-10-33","article-title":"Comparative study of four immortalized human brain capillary endothelial cell lines, hCMEC\/D3, hBMEC, TY10, and BB19, and optimization of culture conditions, for an in vitro blood-brain barrier model for drug permeability studies","volume":"10","author":"Eigenmann","year":"2013","journal-title":"Fluids Barriers CNS"},{"key":"B26","doi-asserted-by":"publisher","first-page":"868407","DOI":"10.3389\/fcimb.2022.868407","article-title":"Vimentin inhibits dengue virus type 2 invasion of the blood-brain barrier","volume":"12","author":"Yu","year":"2022","journal-title":"Front Cell Infect Microbiol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1007\/s00430-007-0065-y","article-title":"Involvement of Escherichia coli K1 ibeT in bacterial adhesion that is associated with the entry into human brain microvascular endothelial cells","volume":"197","author":"Zou","year":"2008","journal-title":"Med Microbiol Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0121911","article-title":"Repositioning of memantine as a potential novel therapeutic agent against meningitic E. coli -induced 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":"B29","doi-asserted-by":"publisher","DOI":"10.1186\/2040-7378-2-13","article-title":"Functional assessments in the rodent stroke model","volume":"2","author":"Schaar","year":"2010","journal-title":"Exp Trans Stroke Med"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1012483","article-title":"Phosphorylated vimentin-triggered fibronectin matrix disaggregation enhances the dissemination of treponema pallidum subsp. Pallidum across the microvascular endothelial barrier","volume":"20","author":"Luo","year":"2024","journal-title":"PloS Pathog"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2010.02.002","article-title":"Improved muscle strength and mobility in the dy(2j)\/dy(2j) mouse with merosin deficient congenital muscular dystrophy treated with glatiramer acetate","volume":"20","author":"Dadush","year":"2010","journal-title":"Neuromuscul. Disord"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dky042","article-title":"Role of bacterial efflux pumps in biofilm formation","volume":"73","author":"Alav","year":"2018","journal-title":"J Antimicrob Chemother"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1126\/science.284.5418.1318","article-title":"Bacterial biofilms: a common cause of persistent infections","volume":"284","author":"Costerton","year":"1999","journal-title":"Science"},{"key":"B34","doi-asserted-by":"publisher","first-page":"186","DOI":"10.26444\/aaem\/85651","article-title":"Streptococcus suis: a re-emerging pathogen associated with occupational exposure to pigs or pork products. Part II - pathogenesis","volume":"25","author":"Dutkiewicz","year":"2018","journal-title":"Ann Agr. Env Med"},{"key":"B35","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s10822-019-00250-8","article-title":"Inhibitor discovery for the E. coli meningitis virulence factor IbeA from homology modeling and virtual screening","volume":"34","author":"Xu","year":"2020","journal-title":"J Comput-Aided. Mol Des"},{"key":"B36","doi-asserted-by":"publisher","first-page":"5389","DOI":"10.1038\/s41467-025-60995-9","article-title":"Structure of lymphostatin, a large multi-functional virulence factor of pathogenic Escherichia coli","volume":"16","author":"Griessmann","year":"2025","journal-title":"Nat Commun"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics14070667","article-title":"Genomic and functional characterization of multidrug-resistant E. coli: insights into resist me, virulome, and signaling systems","volume":"14","author":"Srinivasan","year":"2025","journal-title":"Antibiotics-Basel"},{"key":"B38","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1111\/eva.12431","article-title":"Manipulating virulence factor availability can have complex consequences for infections","volume":"10","author":"Weigert","year":"2017","journal-title":"Evol Appl"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2016.00148","article-title":"Pathogenic triad in bacterial meningitis: pathogen invasion, NF-\u03baB activation, and leukocyte transmigration that occur at the blood-brain barrier","volume":"7","author":"Wang","year":"2016","journal-title":"Front Microbiol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.260509","article-title":"The diverse actions of cytoskeletal vimentin in bacterial infection and host defense","volume":"136","author":"Miao","year":"2023","journal-title":"J Cell Sci"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.250597","article-title":"The diverse roles and dynamic rearrangement of vimentin during viral infection","volume":"134","author":"Zhang","year":"2020","journal-title":"J Cell Sci"},{"key":"B42","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/ncb898","article-title":"Vimentin is secreted by activated macrophages","volume":"5","author":"Mor-Vaknin","year":"2003","journal-title":"Nat Cell Biol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"7287","DOI":"10.1038\/ncomms8287","article-title":"Vimentin filament organization and stress sensing depend on its single cysteine residue and zinc binding","volume":"6","author":"P\u00e9rez-Sala","year":"2015","journal-title":"Nat Commun"},{"key":"B44","doi-asserted-by":"publisher","first-page":"6574","DOI":"10.1038\/ncomms7574","article-title":"Vimentin regulates activation of the NLRP3 inflammasome","volume":"6","author":"Dos Santos","year":"2015","journal-title":"Nat Commun"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3390\/life15101563","article-title":"Oral treatment with the vimentin-targeting compound ALD-r491 mitigates hyperinflammation, multi-organ injury, and mortality in CLP-induced septic mice","volume":"15","author":"Wu","year":"2025","journal-title":"Life (Basel)"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2007.04.010","article-title":"The tumor inhibitor and antiangiogenic agent withaferin a target the intermediate filament protein vimentin","volume":"14","author":"Bargagna-Mohan","year":"2007","journal-title":"Chem Biol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039065","article-title":"Withaferin a alters intermediate filament organization, cell shape and behavior","volume":"7","author":"Grin","year":"2012","journal-title":"PloS One"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2010.100442","article-title":"Glatiramer acetate attenuates pro-inflammatory t cell responses but does not directly protect neurons from inflammatory cell death","volume":"177","author":"Herrmann","year":"2010","journal-title":"Am J Pathol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1578","DOI":"10.3390\/cells11091578","article-title":"Glatiramer acetate immunomodulation: evidence of neuroprotection and cognitive preservation","volume":"11","author":"Kasindi","year":"2022","journal-title":"Cells"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2336171100","article-title":"Glatiramer acetate-specific t cells in the brain express t helper 2\/3 cytokines and brain-derived neurotrophic factor in situ","volume":"100","author":"Aharoni","year":"2003","journal-title":"Proc Natl Acad Sci"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1793594\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T04:20:32Z","timestamp":1776313232000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1793594\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,16]]},"references-count":50,"alternative-id":["10.3389\/fimmu.2026.1793594"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1793594","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,16]]},"article-number":"1793594"}}