Early Invasion of Brain Parenchyma by African Trypanosomes

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dc.contributor.authorFrevert, Uteen
dc.contributor.authorMovila, Alexandruen
dc.contributor.authorNikolskaia, Olga V.en
dc.contributor.authorRaper, Jayneen
dc.contributor.authorMackey, Zachary B.en
dc.contributor.authorAbdulla, Mahaen
dc.contributor.authorMcKerrow, James H.en
dc.contributor.authorGrab, Dennis J.en
dc.contributor.departmentBiochemistryen
dc.date.accessioned2018-06-01T19:04:08Zen
dc.date.available2018-06-01T19:04:08Zen
dc.date.issued2012-08-31en
dc.description.abstractHuman African trypanosomiasis or sleeping sickness is a vector-borne parasitic disease that has a major impact on human health and welfare in sub-Saharan countries. Based mostly on data from animal models, it is currently thought that trypanosome entry into the brain occurs by initial infection of the choroid plexus and the circumventricular organs followed days to weeks later by entry into the brain parenchyma. However, Trypanosoma brucei bloodstream forms rapidly cross human brain microvascular endothelial cells in vitro and appear to be able to enter the murine brain without inflicting cerebral injury. Using a murine model and intravital brain imaging, we show that bloodstream forms of T. b. brucei and T. b. rhodesiense enter the brain parenchyma within hours, before a significant level of microvascular inflammation is detectable. Extravascular bloodstream forms were viable as indicated by motility and cell division, and remained detectable for at least 3 days post infection suggesting the potential for parasite survival in the brain parenchyma. Vascular inflammation, as reflected by leukocyte recruitment and emigration from cortical microvessels, became apparent only with increasing parasitemia at later stages of the infection, but was not associated with neurological signs. Extravascular trypanosomes were predominantly associated with postcapillary venules suggesting that early brain infection occurs by parasite passage across the neuroimmunological blood brain barrier. Thus, trypanosomes can invade the murine brain parenchyma during the early stages of the disease before meningoencephalitis is fully established. Whether individual trypanosomes can act alone or require the interaction from a quorum of parasites remains to be shown. The significance of these findings for disease development is now testable.en
dc.description.versionPublished versionen
dc.format.extent? - ? (11) page(s)en
dc.identifier.doihttps://doi.org/10.1371/journal.pone.0043913en
dc.identifier.issn1932-6203en
dc.identifier.issue8en
dc.identifier.orcidMackey, ZB [0000-0002-4533-0973]en
dc.identifier.urihttp://hdl.handle.net/10919/83436en
dc.identifier.volume7en
dc.language.isoenen
dc.publisherPLOSen
dc.relation.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000308221300033&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=930d57c9ac61a043676db62af60056c1en
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectcentral-nervous-systemen
dc.subjectbrucei-bruceien
dc.subjectsleeping sicknessen
dc.subjectparkinsons-diseaseen
dc.subjectcerebral malariaen
dc.subjectbarrier damageen
dc.subjectvervet monkeysen
dc.subjectblooden
dc.subjectinfectionen
dc.subjectmodelen
dc.titleEarly Invasion of Brain Parenchyma by African Trypanosomesen
dc.title.serialPLOS ONEen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.otherArticleen
dc.type.otherJournalen
pubs.organisational-group/Virginia Techen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciencesen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/Biochemistryen
pubs.organisational-group/Virginia Tech/Agriculture & Life Sciences/CALS T&R Facultyen
pubs.organisational-group/Virginia Tech/All T&R Facultyen
pubs.organisational-group/Virginia Tech/University Research Institutesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciencesen
pubs.organisational-group/Virginia Tech/University Research Institutes/Fralin Life Sciences/Fralin Affiliated Facultyen

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