{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T11:46:45Z","timestamp":1790423205292,"version":"4.1.0"},"reference-count":59,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Extracellular vesicles (EVs) released by bacteria are potent mediators of host\u2013microbe interactions. They modulate immune responses, deliver functional molecules and influence disease progression. However, whether bacterial EVs can access the brain and functionally affect host cells remains unclear. In this study, we engineered\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    \u2010derived EVs by electroporating Cre recombinase mRNA (Ec EV\n                    <jats:sup>Cre<\/jats:sup>\n                    ) and assessed their transport and functional delivery following intranasal administration. Using mT\/mG reporter mice, we observed EV uptake in the olfactory epithelium and recombination\u2010driven GFP expression in a subset of neurons in the olfactory bulb, providing proof\u2010of\u2010concept for the functional delivery of bacterial EV\u2010associated mRNA into the brain. Single\u2010cell RNA sequencing and imaging analyses of the olfactory regions revealed neuronal and immune cell subsets as key EV targets. Microfluidic biochip chamber assays with cultured sensory neurons demonstrated that EVs undergo retrograde axonal transport from neurite terminals to the soma via signalling endosomes. Pharmacological inhibition significantly impaired EV uptake, supporting the involvement of endocytic pathways. In addition to neuronal entry, we discovered that phagocytic cells, including neutrophils and macrophages, can engulf EV\n                    <jats:sup>Cre<\/jats:sup>\n                    in the nasal mucosa and migrate into the brain, providing an alternative immune\u2010mediated route for vesicle delivery. Together, these findings indicate that bacterial EVs exploit both neuronal and phagocytic pathways to deliver functional RNA cargo into the brain, providing novel insights into microbial access to the central nervous system and its implications for neuroimmune interactions.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70320","type":"journal-article","created":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T17:52:07Z","timestamp":1781200327000},"source":"Crossref","is-referenced-by-count":2,"title":["Intranasal Delivery of Bacterial Extracellular Vesicles Enables RNA Cargo Entry Into the Brain"],"prefix":"10.1002","volume":"15","author":[{"given":"Jae Yeong","family":"Ha","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, School of Dentistry Kyungpook National University  Daegu South Korea"},{"name":"Oral\u2010Brain Axis Research Laboratory Kyungpook National University  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So\u2010Mi","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Dentistry Kyungpook National University  Daegu South Korea"},{"name":"Oral\u2010Brain Axis Research Laboratory Kyungpook National University  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song\u2010Yi","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Dentistry Kyungpook National University  Daegu South Korea"},{"name":"Oral\u2010Brain Axis Research Laboratory Kyungpook National University  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanyong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Sensors Korea Institute of Machinery and Materials (KIMM)  Daegu South Korea"},{"name":"School of Integrative Engineering Chung\u2010Ang University  Seoul South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungsu","family":"Park","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering Sungkyunkwan University  Suwon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5569-3826","authenticated-orcid":false,"given":"Su\u2010Hyung","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Dentistry Kyungpook National University  Daegu South Korea"},{"name":"Brain Science &amp; Engineering Institute Kyungpook National University  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Il\u2010Sung","family":"Jang","sequence":"additional","affiliation":[{"name":"Oral\u2010Brain Axis Research Laboratory Kyungpook National University  Daegu South Korea"},{"name":"Brain Science &amp; Engineering Institute Kyungpook National University  Daegu South Korea"},{"name":"Department of Pharmacology, School of Dentistry Kyungpook National University  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youngkyun","family":"Lee","sequence":"additional","affiliation":[{"name":"Oral\u2010Brain Axis Research Laboratory Kyungpook National University  Daegu South Korea"},{"name":"Department of Biochemistry, School of Dentistry Kyungpook National University  Daegu South Korea"},{"name":"Craniofacial Nerve\u2010Bone Network Research Center Kyungpook National University  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1911-5014","authenticated-orcid":false,"given":"Heon\u2010Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, School of Dentistry Kyungpook National University  Daegu South Korea"},{"name":"Oral\u2010Brain Axis Research Laboratory Kyungpook National University  Daegu South Korea"},{"name":"Craniofacial Nerve\u2010Bone Network Research Center Kyungpook National University  Daegu South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2025.1629349"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571\u2010018\u20100609\u20102"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2022.04.012"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jneuroim.2022.577897"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010022\u201006749\u20109"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0805532107"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.288"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370217723166"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25073788"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a020669"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2018"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0706192104"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00118\u201013"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0093338"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010024\u201053279\u20101"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/mcp.M115.051649"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1087057114524278"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12264\u2010017\u20100170\u2010x"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2025.117019"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2022.925435"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2020.596366"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1011743"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201901575R"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010017\u201010229\u2010w"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.0c02346"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1211\/0022357022539"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2023.1227655"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00284\u2010013\u20100411\u20109"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000412"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2015.02.006"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom12091171"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2010.01.032"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1924\u201015.2015"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adt9591"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1177\/1535370220923585"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.12.006"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2014.10.019"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2020.09.007"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010024\u201007125\u20101"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3402\/jev.v3.24641"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvg.20335"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/cmi.12655"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010025\u201003410\u20101"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/sdata.2018.241"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41423\u2010025\u201001333\u20103"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1080\/21645515.2020.1799667"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201075108\u20103"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41577\u2010025\u201001175\u20100"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00025\u201014"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035\u2010020\u201000200\u20107"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873\u20103468.13235"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms12976"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.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