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 language | English |
|---|---|
| Pages (from-to) | 3632-3642 |
| Number of pages | 11 |
| Journal | Journal of Immunology |
| Volume | 185 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 15 Sep 2010 |
Cite this
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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 journal › Article › Research › peer-review
TY - JOUR
T1 - Immune-mediated mechanisms of parasite tissue sequestration during experimental cerebral malaria
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
Y1 - 2010/9/15
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.
UR - http://www.scopus.com/inward/record.url?scp=78649848029&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.1000944
DO - 10.4049/jimmunol.1000944
M3 - Article
C2 - 20720206
AN - SCOPUS:78649848029
VL - 185
SP - 3632
EP - 3642
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 6
ER -