{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T15:01:26Z","timestamp":1775746886443,"version":"3.50.1"},"reference-count":101,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,5,11]],"date-time":"2021-05-11T00:00:00Z","timestamp":1620691200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT\u2010153336"],"award-info":[{"award-number":["PJT\u2010153336"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Microbiology"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Lyme disease is the most common tick\u2010transmitted disease in the northern hemisphere and is caused by the spirochete <jats:italic>Borrelia<\/jats:italic> <jats:italic>burgdorferi<\/jats:italic> and related <jats:italic>Borrelia<\/jats:italic> species. The constellation of symptoms attributable to this malady results from vascular dissemination of <jats:italic>B. burgdorferi<\/jats:italic> throughout the body to invade various tissue types. However, little is known about the mechanism by which the spirochetes can breach the blood vessel wall to reach distant tissues. We have studied this process by direct observation of spirochetes in the microvasculature of living mice using multi\u2010laser spinning\u2010disk intravital microscopy. Our results show that in our experimental system, instead of phagocytizing <jats:italic>B. burgdorferi,<\/jats:italic> host neutrophils are involved in the production of specific cytokines that activate the endothelium and potentiate <jats:italic>B. burgdorferi<\/jats:italic> escape into the surrounding tissue. Spirochete escape is not induced by paracellular permeability and appears to occur via a transcellular pathway. Neutrophil repurposing to promote bacterial extravasation represents a new and innovative pathogenic strategy.<\/jats:p>","DOI":"10.1111\/mmi.14728","type":"journal-article","created":{"date-parts":[[2021,4,23]],"date-time":"2021-04-23T17:08:49Z","timestamp":1619197729000},"page":"498-515","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["The Lyme disease spirochete can hijack the host immune system for extravasation from the microvasculature"],"prefix":"10.1111","volume":"116","author":[{"given":"Xi","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology Snyder Institute for Chronic Diseases University of Calgary Calgary AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bj\u00f6rn","family":"Petri","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology &amp; Infectious Diseases Snyder Institute for Chronic Diseases University of Calgary Calgary AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebekah","family":"DeVinney","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology &amp; Infectious Diseases Snyder Institute for Chronic Diseases University of Calgary Calgary AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig N.","family":"Jenne","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology &amp; Infectious Diseases Snyder Institute for Chronic Diseases University of Calgary Calgary AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9611-2095","authenticated-orcid":false,"given":"George","family":"Chaconas","sequence":"additional","affiliation":[{"name":"Department of Biochemistry &amp; Molecular Biology Snyder Institute for Chronic Diseases University of Calgary Calgary AB Canada"},{"name":"Department of Microbiology, Immunology &amp; Infectious Diseases Snyder Institute for Chronic Diseases University of Calgary Calgary AB Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,5,11]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri1184"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000255691.76142.4a"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000255690.03436.ae"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90524.2008"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells9010043"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/150.4.497"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1718595115"},{"key":"e_1_2_8_9_1","first-page":"145","article-title":"Immune response to Borrelia: Lessons from lyme disease spirochetes","volume":"42","author":"Bockenstedt L.K.","year":"2021","journal-title":"Current Issues in Molecular Biology"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.11.011"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201847046"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110525"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.72.9.4956\u20104965.2004"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.10.5142\u20105150.1999"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rinim.2015.12.001"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.10.4875\u20104883.1998"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.65.4.1217-1222.1997"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2019.01923"},{"key":"e_1_2_8_19_1","first-page":"385","article-title":"Live imaging","volume":"42","author":"Chaconas G.","year":"2020","journal-title":"Current Issues in Molecular Biology"},{"key":"e_1_2_8_20_1","first-page":"473","article-title":"Lyme disease pathogenesis","volume":"42","author":"Coburn J.","year":"2021","journal-title":"Current Issues in Molecular Biology"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.57.5.1626\u20101628.1989"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0882\u20104010(91)90074\u2010K"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro.2016.178"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00186-17"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.0407247"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.GPP3\u20100061\u20102019"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2008.0027"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005682"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.00519"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102018\u201012\u2010844605"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20150718"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041450315"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01409985"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01204-17"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010016\u20101551\u20103"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2007.10.004"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2020.183237"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12882"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/microarrays5020009"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0158019"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0180267"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3399"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184411"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010018\u20102790\u20105"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005333"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.1855"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1404769111"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrmicro2269"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1008516"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20040830"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micinf.2006.08.014"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1201095"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mib.2016.11.008"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.59.2.671\u2010678.1991"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathol\u2010020712\u2010164023"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00012.2005"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1103771"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12171"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000090"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1111\/mmi.12045"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2015.10.006"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/ni.2921"},{"key":"e_1_2_8_63_1","first-page":"253","article-title":"Neutrophils as emerging therapeutic targets","volume":"19","author":"Nemeth T.","year":"2020","journal-title":"Nature Reviews"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000169"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.BAI-0010-2019"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-015-0346-0"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiw355"},{"key":"e_1_2_8_68_1","first-page":"233","article-title":"Innate immunity networks during infection with Borrelia burgdorferi","volume":"42","author":"Oosting M.","year":"2016","journal-title":"Critical Reviews in Microbiology"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2016.10.006"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2016.07.003"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.46.2.608\u2010611.1984"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102010\u201002\u2010270561"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar576"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/apha.12860"},{"key":"e_1_2_8_75_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.5.2660"},{"key":"e_1_2_8_76_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.micro.112408.134040"},{"key":"e_1_2_8_77_1","doi-asserted-by":"publisher","DOI":"10.1080\/21541248.2016.1197872"},{"key":"e_1_2_8_78_1","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.304"},{"key":"e_1_2_8_79_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.64.8.3180\u20103187.1996"},{"key":"e_1_2_8_80_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.63.11.4439\u20104447.1995"},{"key":"e_1_2_8_81_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI74527"},{"key":"e_1_2_8_82_1","doi-asserted-by":"publisher","DOI":"10.1093\/femsre\/fux047"},{"key":"e_1_2_8_83_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2016.90"},{"key":"e_1_2_8_84_1","first-page":"83","article-title":"Regulation of gene and protein expression in the Lyme disease spirochete","volume":"415","author":"Stevenson B.","year":"2018","journal-title":"Current Topics in Microbiology and Immunology"},{"key":"e_1_2_8_85_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.7.3433\u20103435.1998"},{"key":"e_1_2_8_86_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114615"},{"key":"e_1_2_8_87_1","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12952"},{"key":"e_1_2_8_88_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2016.04.003"},{"key":"e_1_2_8_89_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00508"},{"key":"e_1_2_8_90_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/9671604"},{"key":"e_1_2_8_91_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89652"},{"key":"e_1_2_8_92_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.10.3608"},{"key":"e_1_2_8_93_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ttbdis.2020.101638"},{"key":"e_1_2_8_94_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-6-92"},{"key":"e_1_2_8_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3908"},{"key":"e_1_2_8_96_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood\u20102008\u201011\u2010188375"},{"key":"e_1_2_8_97_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.10.4584"},{"key":"e_1_2_8_98_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13984"},{"key":"e_1_2_8_99_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01188-10"},{"key":"e_1_2_8_100_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.8.5109"},{"key":"e_1_2_8_101_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aam8929"},{"key":"e_1_2_8_102_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00787.2001"}],"container-title":["Molecular Microbiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mmi.14728","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/mmi.14728","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/mmi.14728","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T14:47:30Z","timestamp":1692715650000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/mmi.14728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,11]]},"references-count":101,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2021,8]]}},"alternative-id":["10.1111\/mmi.14728"],"URL":"https:\/\/doi.org\/10.1111\/mmi.14728","archive":["Portico"],"relation":{},"ISSN":["0950-382X","1365-2958"],"issn-type":[{"value":"0950-382X","type":"print"},{"value":"1365-2958","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,11]]},"assertion":[{"value":"2021-02-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-04-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-05-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}