{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T16:39:59Z","timestamp":1777567199734,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0005765","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:00:00Z","timestamp":1501718400000}}],"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2017,7,24]],"date-time":"2017-07-24T00:00:00Z","timestamp":1500854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21 AI117368"],"award-info":[{"award-number":["R21 AI117368"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R21 AI126343"],"award-info":[{"award-number":["R21 AI126343"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"John W. McLaughlin","award":["McLaughlin Postdoctoral Fellowship"],"award-info":[{"award-number":["McLaughlin Postdoctoral Fellowship"]}]},{"name":"Health Department of Henan Province and the People's Hospital of Henan Province","award":["Research Fellowship"],"award-info":[{"award-number":["Research Fellowship"]}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T35 AI078878"],"award-info":[{"award-number":["T35 AI078878"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["T32 AI060549"],"award-info":[{"award-number":["T32 AI060549"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R25 GM069285"],"award-info":[{"award-number":["R25 GM069285"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["P30 ES006676"],"award-info":[{"award-number":["P30 ES006676"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"DOI":"10.1371\/journal.pntd.0005765","type":"journal-article","created":{"date-parts":[[2017,7,24]],"date-time":"2017-07-24T13:46:06Z","timestamp":1500903966000},"page":"e0005765","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":36,"title":["Type 1-skewed neuroinflammation and vascular damage associated with Orientia tsutsugamushi infection in mice"],"prefix":"10.1371","volume":"11","author":[{"given":"Lynn","family":"Soong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6686-6032","authenticated-orcid":true,"given":"Thomas R.","family":"Shelite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Xing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harica","family":"Kodakandla","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuejin","family":"Liang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brandon J.","family":"Trent","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulina","family":"Horton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn C.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenyang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaren","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donald H.","family":"Bouyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiyang","family":"Cai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2017,7,24]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"e0004161","DOI":"10.1371\/journal.pntd.0004161","article-title":"A spatiotemporal database to track human scrub typhus using the VectorMap application","volume":"9","author":"DJ Kelly","year":"2015","journal-title":"PLoS Negl Trop Dis"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"301","DOI":"10.4269\/ajtmh.13-0064","article-title":"Unresolved problems related to scrub typhus: a seriously neglected life-threatening disease","volume":"89","author":"DH Paris","year":"2013","journal-title":"Am J Trop Med Hyg"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1016\/S1995-7645(12)60036-4","article-title":"Scrub typhus: pathophysiology, clinical manifestations and prognosis","volume":"5","author":"S Rajapakse","year":"2012","journal-title":"Asian Pac J Trop Med"},{"key":"ref4","article-title":"Increased endothelial and macrophage markers are associated with disease severity and mortality in scrub typhus","author":"K Otterdal","year":"2014","journal-title":"J Infect"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"131","DOI":"10.4103\/0972-2327.107701","article-title":"Neurological manifestations of scrub typhus","volume":"16","author":"S Gulati","year":"2013","journal-title":"Ann Indian Acad Neurol"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"453","DOI":"10.4103\/0972-5229.136074","article-title":"Acute encephalitis syndrome following scrub typhus infection","volume":"18","author":"A Kar","year":"2014","journal-title":"Indian J Crit Care Med"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1186\/s13104-015-1428-x","article-title":"Scrub typhus mimicking Parkinson&apos;s disease","volume":"8","author":"R Premaratna","year":"2015","journal-title":"BMC Res Notes"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1177\/0049475516636543","article-title":"Neurological manifestations of scrub typhus in adults","volume":"47","author":"A Rana","year":"2017","journal-title":"Trop Doct"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1007\/s12098-015-2001-2","article-title":"CNS manifestations in <italic>Orientia tsutsugamushi<\/italic> disease (scrub typhus) in north India","volume":"83","author":"AK Sood","year":"2016","journal-title":"Indian J Pediatr"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"36","DOI":"10.3988\/jcn.2008.4.1.36","article-title":"Polyneuropathy and cerebral infarction complicating scrub typhus","volume":"4","author":"JH Kim","year":"2008","journal-title":"J Clin Neurol"},{"key":"ref11","first-page":"706","article-title":"Abducens nerve palsy in a patient with scrub typhus: a case report","volume":"30","author":"B Bhardwaj","year":"2013","journal-title":"Trop Biomed"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"163","DOI":"10.4103\/2141-9248.157486","article-title":"Tsutsugamushi disease (scrub typhus) meningoencephalitis in north eastern India: A prospective study","volume":"5","author":"SR Sharma","year":"2015","journal-title":"Ann Med Health Sci Res"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"e104","DOI":"10.1016\/S2214-109X(14)70289-X","article-title":"Orientia, rickettsia, and leptospira pathogens as causes of CNS infections in Laos: a prospective study","volume":"3","author":"S Dittrich","year":"2015","journal-title":"Lancet Glob Health"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1136\/jnnp-2014-308722","article-title":"Neurological manifestations of scrub typhus","volume":"86","author":"UK Misra","year":"2015","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"e3064","DOI":"10.1371\/journal.pntd.0003064","article-title":"Dissemination of <italic>Orientia tsutsugamushi<\/italic> and inflammatory responses in a murine model of scrub typhus","volume":"8","author":"CA Keller","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"e0004884","DOI":"10.1371\/journal.pntd.0004884","article-title":"An intradermal inoculation mouse model for immunological investigations of acute scrub typhus and persistent infection","volume":"10","author":"L Soong","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"e2966","DOI":"10.1371\/journal.pntd.0002966","article-title":"A hematogenously disseminated <italic>Orientia tsutsugamushi<\/italic>-infected murine model of scrub typhus","volume":"8","author":"TR Shelite","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"e3191","DOI":"10.1371\/journal.pntd.0003191","article-title":"Strong type 1, but impaired type 2, immune responses contribute to <italic>Orientia tsutsugamushi<\/italic>-induced pathology in mice","volume":"8","author":"L Soong","year":"2014","journal-title":"PLoS Negl Trop Dis"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"e0004467","DOI":"10.1371\/journal.pntd.0004467","article-title":"IL-33-dependent endothelial activation contributes to apoptosis and renal injury in <italic>Orientia tsutsugamushi<\/italic>-infected mice","volume":"10","author":"TR Shelite","year":"2016","journal-title":"PLoS Negl Trop Dis"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1258\/002367788780864457","article-title":"Lectins as markers of endothelial cells: comparative study between human and animal cells","volume":"22","author":"F Roussel","year":"1988","journal-title":"Lab Anim"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1084\/jem.20150718","article-title":"Interfering with VE-PTP stabilizes endothelial junctions in vivo via Tie-2 in the absence of VE-cadherin","volume":"212","author":"M Frye","year":"2015","journal-title":"J Exp Med"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"2472","DOI":"10.1073\/pnas.1519467113","article-title":"Gene control of tyrosine kinase TIE2 and vascular manifestations of infections","volume":"113","author":"CC Ghosh","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1007\/s00429-016-1267-0","article-title":"Different segments of the cerebral vasculature reveal specific endothelial specifications, while tight junction proteins appear equally distributed","volume":"222","author":"S Hanske","year":"2017","journal-title":"Brain Struct Funct"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"e1028","DOI":"10.1371\/journal.pntd.0001028","article-title":"<italic>Orientia tsutsugamushi<\/italic> stimulates an original gene expression program in monocytes: relationship with gene expression in patients with scrub typhus","volume":"5","author":"W Tantibhedhyangkul","year":"2011","journal-title":"PLoS Negl Trop Dis"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/j.micpath.2012.10.001","article-title":"<italic>Orientia tsutsugamushi<\/italic>, the causative agent of scrub typhus, induces an inflammatory program in human macrophages","volume":"55","author":"W Tantibhedhyangkul","year":"2012","journal-title":"Microb Pathog"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.micpath.2010.05.001","article-title":"<italic>Orientia tsutsugamushi<\/italic> induced endothelial cell activation via the NOD1-IL-32 pathway","volume":"49","author":"KA Cho","year":"2010","journal-title":"Microb Pathog"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"e39042","DOI":"10.1371\/journal.pone.0039042","article-title":"Intracellular invasion of <italic>Orientia tsutsugamushi<\/italic> activates inflammasome in ASC-dependent manner","volume":"7","author":"JE Koo","year":"2012","journal-title":"PLoS One"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/j.micinf.2011.03.003","article-title":"Subversion of host cell signaling by <italic>Orientia tsutsugamushi<\/italic>","volume":"13","author":"Y Ge","year":"2011","journal-title":"Microbes Infect"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1128\/IAI.00185-16","article-title":"Toll-like receptor 2 recognizes <italic>Orientia tsutsugamushi<\/italic> and increases susceptibility to murine experimental scrub typhus","volume":"84","author":"M Gharaibeh","year":"2016","journal-title":"Infect Immun"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1159\/000334245","article-title":"Dendritic cells and damage-associated molecular patterns: endogenous danger signals linking innate and adaptive immunity","volume":"4","author":"G Nace","year":"2011","journal-title":"J Innate Immun"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.2741\/s215","article-title":"RAGE during infectious diseases","volume":"3","author":"MA van Zoelen","year":"2011","journal-title":"Front Biosci (Schol Ed)"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/j.molimm.2013.07.008","article-title":"RAGE and TLRs: relatives, friends or neighbours?","volume":"56","author":"ZA Ibrahim","year":"2013","journal-title":"Mol Immunol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"219","DOI":"10.3390\/diagnostics5020219","article-title":"Circulating HMGB1 and RAGE as clinical biomarkers in malignant and autoimmune diseases","volume":"5","author":"C Pilzweger","year":"2015","journal-title":"Diagnostics (Basel)"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.clim.2011.11.007","article-title":"Interleukin-33 upregulation in peripheral leukocytes and CNS of multiple sclerosis patients","volume":"142","author":"GP Christophi","year":"2012","journal-title":"Clin Immunol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/j.neuron.2015.01.013","article-title":"The glia-derived alarmin IL-33 orchestrates the immune response and promotes recovery following CNS injury","volume":"85","author":"SP Gadani","year":"2015","journal-title":"Neuron"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/j.immuni.2015.02.019","article-title":"CNS injury: IL-33 sounds the alarm","volume":"42","author":"SL Foster","year":"2015","journal-title":"Immunity"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1084\/jem.20161982","article-title":"Characterization of meningeal type 2 innate lymphocytes and their response to CNS injury","volume":"214","author":"SP Gadani","year":"2017","journal-title":"J Exp Med"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.neuron.2015.05.019","article-title":"Dealing with danger in the CNS: the response of the immune system to injury","volume":"87","author":"SP Gadani","year":"2015","journal-title":"Neuron"},{"key":"ref39","first-page":"603","article-title":"A comparative study of the pathology of scrub typhus (tsutsugamushi disease) and other rickettsial diseases","volume":"21","author":"AC Allen","year":"1945","journal-title":"Am J Pathol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1038\/modpathol.3880385","article-title":"Identification of the target cells of <italic>Orientia tsutsugamushi<\/italic> in human cases of scrub typhus","volume":"14","author":"CG Moron","year":"2001","journal-title":"Mod Pathol"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"231","DOI":"10.3346\/jkms.2012.27.3.231","article-title":"Persistence of <italic>Orientia tsutsugamushi<\/italic> in humans","volume":"27","author":"MH Chung","year":"2012","journal-title":"J Korean Med Sci"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/S0002-9440(10)63494-3","article-title":"Expression analysis of the T-cell-targeting chemokines CXCL9 and CXCL10 in mice and humans with endothelial infections caused by rickettsiae of the spotted fever group","volume":"163","author":"G Valbuena","year":"2003","journal-title":"Am J Pathol"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1767","DOI":"10.4049\/jimmunol.175.3.1767","article-title":"Opposing effects of CXCR3 and CCR5 deficiency on CD8<sup>+<\/sup> T cell-mediated inflammation in the central nervous system of virus-infected mice","volume":"175","author":"C de Lemos","year":"2005","journal-title":"J Immunol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1089\/vim.2008.0057","article-title":"Unaltered neurological disease and mortality in CXCR3-deficient mice infected intracranially with lymphocytic choriomeningitis virus-Armstrong","volume":"21","author":"MJ Hofer","year":"2008","journal-title":"Viral Immunol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.jneuroim.2014.08.005","article-title":"Enhanced resistance of CXCR3 deficient mice to ocular HSV-1 infection is due to control of replication in the brain ependyma","volume":"276","author":"CM Kroll","year":"2014","journal-title":"J Neuroimmunol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"e1142492","DOI":"10.1080\/21688370.2016.1142492","article-title":"Viral interactions with the blood-brain barrier: old dog, new tricks","volume":"4","author":"J Hou","year":"2016","journal-title":"Tissue Barriers"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.4269\/ajtmh.13-0224","article-title":"Scrub typhus meningitis or meningoencephalitis","volume":"89","author":"DM Kim","year":"2013","journal-title":"Am J Trop Med Hyg"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1002\/jcp.25575","article-title":"Endothelial STAT3 activation increases vascular leakage through downregulating tight junction proteins: implications for diabetic retinopathy","volume":"232","author":"JH Yun","year":"2017","journal-title":"J Cell Physiol"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/S1607-551X(08)70103-7","article-title":"Immunohistochemical study of scrub typhus: a report of two cases","volume":"24","author":"BY Tseng","year":"2008","journal-title":"Kaohsiung J Med Sci"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1111\/nyas.12855","article-title":"The complex contribution of chemokines to neuroinflammation: switching from beneficial to detrimental effects","volume":"1351","author":"O Le Thuc","year":"2015","journal-title":"Ann N Y Acad Sci"}],"updated-by":[{"DOI":"10.1371\/journal.pntd.0005765","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2017,8,3]],"date-time":"2017-08-03T00:00:00Z","timestamp":1501718400000}}],"container-title":["PLOS Neglected Tropical Diseases"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pntd.0005765","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T15:53:28Z","timestamp":1539964408000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pntd.0005765"}},"subtitle":[],"editor":[{"given":"Joseph M.","family":"Vinetz","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2017,7,24]]},"references-count":50,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2017,7,24]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pntd.0005765","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.pntd.0005765","asserted-by":"object"}]},"ISSN":["1935-2735"],"issn-type":[{"value":"1935-2735","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,24]]}}}