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dc.contributor.authorH. Amante, Fionaen_US
dc.contributor.authorHaque, Ashrafulen_US
dc.contributor.authorC. Stanley, Amandaen_US
dc.contributor.authorLabastida Rivera, Fabianen_US
dc.contributor.authorM. Randall, Louiseen_US
dc.contributor.authorA. Wilson, Yanaen_US
dc.contributor.authorYeo, Gladysen_US
dc.contributor.authorPieper, Christianen_US
dc.contributor.authorS. Crabb, Brendanen_US
dc.contributor.authorF. de Koning-Ward, Taniaen_US
dc.contributor.authorJ. Lundie, Rachelen_US
dc.contributor.authorF. Good, Michaelen_US
dc.contributor.authorPinzon-Charry, Albertoen_US
dc.contributor.authorS. Pearson, Marken_US
dc.contributor.authorG. Duke, Maryen_US
dc.contributor.authorP. McManus, Donalden_US
dc.contributor.authorLoukas, Alexen_US
dc.contributor.authorR. Hill, Geoffen_US
dc.contributor.authorR. Engwerda, Christianen_US
dc.description.abstractCerebral malaria is a severe complication of malaria. Sequestration of parasitized RBCs in brain microvasculature is associated with disease pathogenesis, but our understanding of this process is incomplete. In this study, we examined parasite tissue sequestration in an experimental model of cerebral malaria (ECM). We show that a rapid increase in parasite biomass is strongly associated with the induction of ECM, mediated by IFN-? and lymphotoxin a, whereas TNF and IL-10 limit this process. Crucially, we discovered that host CD4+ and CD8+ T cells promote parasite accumulation in vital organs, including the brain. Modulation of CD4+ T cell responses by helminth coinfection amplified CD4+ T cell-mediated parasite sequestration, whereas vaccination could generate CD4+ T cells that reduced parasite biomass and prevented ECM. These findings provide novel insights into immune-mediated mechanisms of ECM pathogenesis and highlight the potential of T cells to both prevent and promote infectious diseases.en_US
dc.publisherAmerican Association of Immunologistsen_US
dc.publisher.placeUnited Statesen_US
dc.relation.ispartofjournalJournal of Immunologyen_US
dc.subject.fieldofresearchImmunology not elsewhere classifieden_US
dc.titleImmune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malariaen_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Peer Reviewed (HERDC)en_US
dc.type.codeC - Journal Articlesen_US
gro.rights.copyrightSelf-archiving of the author-manuscript version is not yet supported by this journal. Please refer to the journal link for access to the definitive, published version or contact the author[s] for more information.en_AU
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