Pathogenesis of cerebral malaria: Recent experimental data and possible applications for humans

J. Lou, R. Lucas, G. E. Grau

Research output: Contribution to journalReview article

178 Citations (Scopus)

Abstract

Malaria still is a major public health problem, partly because the pathogenesis of its major complication, cerebral malaria, remains incompletely understood. Experimental models represent useful tools to better understand the mechanisms of this syndrome. Here, data generated by several models are reviewed both in vivo and in vitro; we propose that some pathogenic mechanisms, drawn from data obtained from experiments in a mouse model, may be instrumental in humans. In particular, tumor necrosis factor (TNF) receptor 2 is involved in this syndrome, implying that the transmembrane form of TNF may be more important than the soluble form of the cytokine. It has also been shown that in addition to differences in immune responsiveness between genetically resistant and susceptible mice, there are marked differences at the level of the target cell of the lesion, namely, the brain endothelial cell. In murine cerebral malaria, a paradoxical role of platelets has been proposed. Indeed, platelets appear to be pathogenic rather than protective in inflammatory conditions because they can potentiate the deleterious effects of TNF. More recently, it has been shown that interactions among platelets, leukocytes, and endothelial cells have phenotypic and functional consequences for the endothelial cells. A better understanding of these complex interactions leading to vascular injury will help improve the outcome of cerebral malaria.

Original languageEnglish (US)
Pages (from-to)810-820
Number of pages11
JournalClinical Microbiology Reviews
Volume14
Issue number4
DOIs
StatePublished - Oct 30 2001

Fingerprint

Cerebral Malaria
Blood Platelets
Endothelial Cells
Tumor Necrosis Factor-alpha
Receptors, Tumor Necrosis Factor, Type II
Vascular System Injuries
Malaria
Leukocytes
Theoretical Models
Public Health
Cytokines
Brain

ASJC Scopus subject areas

  • Epidemiology
  • Immunology and Microbiology(all)
  • Public Health, Environmental and Occupational Health
  • Microbiology (medical)
  • Infectious Diseases

Cite this

Pathogenesis of cerebral malaria : Recent experimental data and possible applications for humans. / Lou, J.; Lucas, R.; Grau, G. E.

In: Clinical Microbiology Reviews, Vol. 14, No. 4, 30.10.2001, p. 810-820.

Research output: Contribution to journalReview article

@article{778a2be2012f4a91bc957b385abbc290,
title = "Pathogenesis of cerebral malaria: Recent experimental data and possible applications for humans",
abstract = "Malaria still is a major public health problem, partly because the pathogenesis of its major complication, cerebral malaria, remains incompletely understood. Experimental models represent useful tools to better understand the mechanisms of this syndrome. Here, data generated by several models are reviewed both in vivo and in vitro; we propose that some pathogenic mechanisms, drawn from data obtained from experiments in a mouse model, may be instrumental in humans. In particular, tumor necrosis factor (TNF) receptor 2 is involved in this syndrome, implying that the transmembrane form of TNF may be more important than the soluble form of the cytokine. It has also been shown that in addition to differences in immune responsiveness between genetically resistant and susceptible mice, there are marked differences at the level of the target cell of the lesion, namely, the brain endothelial cell. In murine cerebral malaria, a paradoxical role of platelets has been proposed. Indeed, platelets appear to be pathogenic rather than protective in inflammatory conditions because they can potentiate the deleterious effects of TNF. More recently, it has been shown that interactions among platelets, leukocytes, and endothelial cells have phenotypic and functional consequences for the endothelial cells. A better understanding of these complex interactions leading to vascular injury will help improve the outcome of cerebral malaria.",
author = "J. Lou and R. Lucas and Grau, {G. E.}",
year = "2001",
month = "10",
day = "30",
doi = "10.1128/CMR.14.4.810-820.2001",
language = "English (US)",
volume = "14",
pages = "810--820",
journal = "Clinical Microbiology Reviews",
issn = "0893-8512",
publisher = "American Society for Microbiology",
number = "4",

}

TY - JOUR

T1 - Pathogenesis of cerebral malaria

T2 - Recent experimental data and possible applications for humans

AU - Lou, J.

AU - Lucas, R.

AU - Grau, G. E.

PY - 2001/10/30

Y1 - 2001/10/30

N2 - Malaria still is a major public health problem, partly because the pathogenesis of its major complication, cerebral malaria, remains incompletely understood. Experimental models represent useful tools to better understand the mechanisms of this syndrome. Here, data generated by several models are reviewed both in vivo and in vitro; we propose that some pathogenic mechanisms, drawn from data obtained from experiments in a mouse model, may be instrumental in humans. In particular, tumor necrosis factor (TNF) receptor 2 is involved in this syndrome, implying that the transmembrane form of TNF may be more important than the soluble form of the cytokine. It has also been shown that in addition to differences in immune responsiveness between genetically resistant and susceptible mice, there are marked differences at the level of the target cell of the lesion, namely, the brain endothelial cell. In murine cerebral malaria, a paradoxical role of platelets has been proposed. Indeed, platelets appear to be pathogenic rather than protective in inflammatory conditions because they can potentiate the deleterious effects of TNF. More recently, it has been shown that interactions among platelets, leukocytes, and endothelial cells have phenotypic and functional consequences for the endothelial cells. A better understanding of these complex interactions leading to vascular injury will help improve the outcome of cerebral malaria.

AB - Malaria still is a major public health problem, partly because the pathogenesis of its major complication, cerebral malaria, remains incompletely understood. Experimental models represent useful tools to better understand the mechanisms of this syndrome. Here, data generated by several models are reviewed both in vivo and in vitro; we propose that some pathogenic mechanisms, drawn from data obtained from experiments in a mouse model, may be instrumental in humans. In particular, tumor necrosis factor (TNF) receptor 2 is involved in this syndrome, implying that the transmembrane form of TNF may be more important than the soluble form of the cytokine. It has also been shown that in addition to differences in immune responsiveness between genetically resistant and susceptible mice, there are marked differences at the level of the target cell of the lesion, namely, the brain endothelial cell. In murine cerebral malaria, a paradoxical role of platelets has been proposed. Indeed, platelets appear to be pathogenic rather than protective in inflammatory conditions because they can potentiate the deleterious effects of TNF. More recently, it has been shown that interactions among platelets, leukocytes, and endothelial cells have phenotypic and functional consequences for the endothelial cells. A better understanding of these complex interactions leading to vascular injury will help improve the outcome of cerebral malaria.

UR - http://www.scopus.com/inward/record.url?scp=0034761722&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034761722&partnerID=8YFLogxK

U2 - 10.1128/CMR.14.4.810-820.2001

DO - 10.1128/CMR.14.4.810-820.2001

M3 - Review article

C2 - 11585786

AN - SCOPUS:0034761722

VL - 14

SP - 810

EP - 820

JO - Clinical Microbiology Reviews

JF - Clinical Microbiology Reviews

SN - 0893-8512

IS - 4

ER -