Immunopathological changes in human cerebral malaria.
Pathogenic mechanisms in human cerebral malaria remain unclear. We reevaluate the role of cell-mediated immune mechanisms in the pathogenesis of this disease based on autopsy findings in a 34-year-old Caucasian male. Histologic examination of brain tissue showed typical features of severe malaria infection (sequestration of Plasmodium falciparum-infected erythrocytes in vessels, cerebral oedema, petechial lesions and Dürck granulomas). In addition to these classical changes, we found that leukocytes that stained positively in immunohistochemistry for CD68 and tumor necrosis factor-alpha (TNF) coexisted with infected erythrocytes in capillaries, whereas in venules the monocyte population outnumbered the erythrocytes. Notable expression of ICAM-1 on endothelial cell surface was detected by immunohistochemistry in vessels with sequestered cells but not in unaffected vessels. These changes are identical to those of the murine model of the disease, in which cell-mediated immune mechanisms and TNF have been implicated. In vitro, ICAM-1 has been shown to be a potential ligand for P. falciparum-infected erythrocytes. In malaria patients, high serum TNF levels, which have been detected in close correlation with disease severity, may thus favor adhesion to endothelial cells of either red or white blood cells via enhanced ICAM-1 expression. The present observations are further evidence for a role of cell-mediated immunity in the pathogenesis of human cerebral malaria.
Porta
J
J
Department of Pathology, CMU, University of Geneva, Switzerland.
Carota
A
A
Pizzolato
G P
GP
Wildi
E
E
Widmer
M C
MC
Margairaz
C
C
Grau
G E
GE
D017088:AIDS-Related Opportunistic Infections / Q000276:immunology / Q000473:pathology*; D000328:Adult; D001921:Brain / Q000098:blood supply; D002196:Capillaries / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000032:analysis*; D002543:Cerebral Hemorrhage / Q000473:pathology; D004730:Endothelium, Vascular / Q000473:pathology; D004912:Erythrocytes / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D018799:Intercellular Adhesion Molecule-1; D016779:Malaria, Cerebral / Q000276:immunology / Q000473:pathology*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D015815:Cell Adhesion Molecules; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1