Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria

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Title Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria
Author Amante, Fiona H.; Haque, Ashraful; Stanley, Amanda C.; Rivera, Fabian de Labastida; Randall, Louise M.; Wilson, Yana A.; Yeo, Gladys; Pieper, Christian; Crabb, Brendan S.; Koning-Ward, Tania F. de; Lundie, Rachel J.; Good, Michael Francis; Pinzon-Charry, Alberto; Pearson, Mark S.; Duke, Mary G.; McManus, Donald P.; Loukas, Alex; Hill, Geoff R.; Engwerda, Christian R.
Journal Name Journal of Immunology
Year Published 2010
Place of publication United States
Publisher American Association of Immunologists
Abstract Cerebral 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-γ and lymphotoxin α, 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.
Peer Reviewed Yes
Published Yes
Publisher URI
Copyright Statement Self-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.
Volume 185
Issue Number 6
Page from 3632
Page to 3642
ISSN 0022-1767
Date Accessioned 2011-07-14
Language en_AU
Research Centre Institute for Glycomics
Faculty Faculty of Science, Environment, Engineering and Technology
Subject Immunology
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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