Abstract
Experimental cerebral malaria (ECM) resulting from Plasmodium berghei ANKA infection involves T lymphocytes. However, the mechanisms of T cell-mediated pathogenesis remain unknown. We found that, in contrast to ECM-susceptible C57BL6 mice, perforin-deficient (PFP-KO) mice were resistant to ECM in the absence of brain lesions, whereas cytoadherence of parasitized erythrocytes and massive accumulation of activated/effector CD8 lymphocytes were observed in both groups of mice. ECM is induced in PFP-KO mice after adoptive transfer of cytotoxic CD8+ cells from infected C57BL6 mice, which were directed to the brain of PFP-KO mice. This specific recruitment might involve chemokine/chemokine receptors, since their expression was up-regulated on activated CD8 cells, and susceptibility to ECM was delayed in CCR5-KO mice. Thus, lymphocyte cytotoxicity and cell trafficking are key players in ECM pathogenesis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adoptive Transfer
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Animals
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Brain / immunology*
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Brain / metabolism
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Brain / parasitology
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Brain / pathology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / pathology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Movement / genetics
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Cell Movement / immunology*
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Female
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Fluoresceins / metabolism
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Genetic Predisposition to Disease
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Immunity, Innate / genetics
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Immunologic Memory / genetics
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Malaria, Cerebral / genetics
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Malaria, Cerebral / immunology*
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Malaria, Cerebral / pathology*
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Membrane Glycoproteins / deficiency
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Perforin
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Plasmodium berghei / immunology*
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Plasmodium berghei / pathogenicity
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Pore Forming Cytotoxic Proteins
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Receptors, CCR5 / biosynthesis
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Receptors, CCR5 / deficiency
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Receptors, CCR5 / genetics
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Spleen / chemistry
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Spleen / cytology
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Spleen / immunology
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Spleen / transplantation
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Succinimides / metabolism
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocyte Subsets / pathology
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Cytotoxic / metabolism
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T-Lymphocytes, Cytotoxic / pathology*
Substances
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5-(6)-carboxyfluorescein diacetate succinimidyl ester
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Fluoresceins
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Membrane Glycoproteins
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Pore Forming Cytotoxic Proteins
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Receptors, CCR5
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Succinimides
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Perforin