Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria

Fiona H Amante, Ashraful K M Nazmul Haque, Amanda C Stanley, Fabian De Labastida Rivera, Louise M Randall, Yana A Wilson, Gladys Yeo, Christian Pieper, Brendan S. Crabb, Tania F de Koning-Ward, Rachel J. Lundie, Michael F. Good, Alberto Pinzon-Charry, Mark S Pearson, Mary G. Duke, Donald P McManus, Alex Loukas, Geoff R. Hill, Christian R Engwerda

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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.

Original languageEnglish
Pages (from-to)3632-3642
Number of pages11
JournalJournal of Immunology
Volume185
Issue number6
DOIs
Publication statusPublished - 15 Sep 2010

Cite this

Amante, F. H., Haque, A. K. M. N., Stanley, A. C., Rivera, F. D. L., Randall, L. M., Wilson, Y. A., ... Engwerda, C. R. (2010). Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria. Journal of Immunology, 185(6), 3632-3642. https://doi.org/10.4049/jimmunol.1000944
Amante, Fiona H ; Haque, Ashraful K M Nazmul ; Stanley, Amanda C ; Rivera, Fabian De Labastida ; Randall, Louise M ; Wilson, Yana A ; Yeo, Gladys ; Pieper, Christian ; Crabb, Brendan S. ; de Koning-Ward, Tania F ; Lundie, Rachel J. ; Good, Michael F. ; Pinzon-Charry, Alberto ; Pearson, Mark S ; Duke, Mary G. ; McManus, Donald P ; Loukas, Alex ; Hill, Geoff R. ; Engwerda, Christian R. / Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria. In: Journal of Immunology. 2010 ; Vol. 185, No. 6. pp. 3632-3642.
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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.",
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Amante, FH, Haque, AKMN, Stanley, AC, Rivera, FDL, Randall, LM, Wilson, YA, Yeo, G, Pieper, C, Crabb, BS, de Koning-Ward, TF, Lundie, RJ, Good, MF, Pinzon-Charry, A, Pearson, MS, Duke, MG, McManus, DP, Loukas, A, Hill, GR & Engwerda, CR 2010, 'Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria', Journal of Immunology, vol. 185, no. 6, pp. 3632-3642. https://doi.org/10.4049/jimmunol.1000944

Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria. / Amante, Fiona H; Haque, Ashraful K M Nazmul; Stanley, Amanda C; Rivera, Fabian De Labastida; Randall, Louise M; Wilson, Yana A; Yeo, Gladys; Pieper, Christian; Crabb, Brendan S.; de Koning-Ward, Tania F; Lundie, Rachel J.; Good, Michael F.; Pinzon-Charry, Alberto; Pearson, Mark S; Duke, Mary G.; McManus, Donald P; Loukas, Alex; Hill, Geoff R.; Engwerda, Christian R.

In: Journal of Immunology, Vol. 185, No. 6, 15.09.2010, p. 3632-3642.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Amante, Fiona H

AU - Haque, Ashraful K M Nazmul

AU - Stanley, Amanda C

AU - Rivera, Fabian De Labastida

AU - Randall, Louise M

AU - Wilson, Yana A

AU - Yeo, Gladys

AU - Pieper, Christian

AU - Crabb, Brendan S.

AU - de Koning-Ward, Tania F

AU - Lundie, Rachel J.

AU - Good, Michael F.

AU - Pinzon-Charry, Alberto

AU - Pearson, Mark S

AU - Duke, Mary G.

AU - McManus, Donald P

AU - Loukas, Alex

AU - Hill, Geoff R.

AU - Engwerda, Christian R

PY - 2010/9/15

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N2 - 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.

AB - 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.

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U2 - 10.4049/jimmunol.1000944

DO - 10.4049/jimmunol.1000944

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VL - 185

SP - 3632

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JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

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Amante FH, Haque AKMN, Stanley AC, Rivera FDL, Randall LM, Wilson YA et al. Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria. Journal of Immunology. 2010 Sep 15;185(6):3632-3642. https://doi.org/10.4049/jimmunol.1000944