Role of ICAM-1 (CD54) in the development of murine cerebral malaria.
In susceptible mouse strains, infection of mice with Plasmodium berghei ANKA (PbA) results in a lethal complication, cerebral malaria. Cerebral malaria is due to the immune response induced by the parasite, which results in an increased production of TNF, known to increase the expression of adhesion molecules on the endothelia. To investigate the role of the adhesion molecule ICAM-1 (CD54), we infected wild-type (+/+) and ICAM-1-deficient (-/-) mice with PbA. While +/+ mice died 6-8 days after infection, -/- mice survived > 15 days. Parasitaemia was similar in +/+ and -/- mice. Serum TNF concentration was increased by the infection and was significantly higher in infected +/+ than in -/- mice. However, TNF mRNA levels in spleen, lungs, and brain were elevated in both infected +/+ and -/- mice. For IFN-gamma, serum levels were similar in both groups. A breakdown of the blood-brain barrier was evident in infected +/+ mice only. Interestingly, thrombocytopenia was profound in infected +/+, but practically absent in -/- mice. Moreover, macrophage sequestration was evident in brain venules and lung capillaries of +/+ mice and was significantly less important in the alveolar capillaries of infected -/- mice. In contrast, neutrophil sequestration in the lung was similar in both +/+ and -/- mice. Sequestration of parasitized red blood cells was significantly greater in the alveolar capillaries from +/+ than -/- mice. These results indicate that while the immune response is similar in both +/+ and ICAM-1(-/-) mice, the absence of mortality in ICAM(-/-) mice correlates with a decrease of macrophage and parasitized RBC trapping and a less severe thrombocytopenia.
Favre
N
N
Department of Medical Parasitology, Swiss Tropical Institute, Postfach, CH-4002 Basel, Switzerland.
Da Laperousaz
C
C
Ryffel
B
B
Weiss
N A
NA
Imhof
B A
BA
Rudin
W
W
Lucas
R
R
Piguet
P F
PF
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000378:metabolism; D007962:Leukocytes / Q000502:physiology; D008168:Lung / Q000276:immunology; D008264:Macrophages / Q000502:physiology; D016779:Malaria, Cerebral / Q000097:blood / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009566:Nitrates / Q000097:blood; D018512:Parasitemia; D010962:Plasmodium berghei / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D009566:Nitrates; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma