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Title

Role of CD40-CVD40L in mouse severe malaria

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Published in The American Journal of Pathology. 2001, vol. 159, no. 2, p. 733-42
Abstract We explored the role of CD40-CD40L (CD154) in the severe malaria elicited by Plasmodium berghei anka infection in mice. Mortality was >90% by day 8 after infection in +/+ mice, but markedly decreased in CD40-/- or in CD40L-/- mice, as well as in +/+ mice treated with anti-CD40L monoclonal antibody. Parasitemia was similar in the different conditions. Breakdown of the blood-brain barrier was evident in infected +/+, but not in CD40-/- mice. Thrombocytopenia was less severe in CD40-/- mice than in the +/+ controls. Sequestration of macrophages in brain venules and alveolar capillaries was reduced in CD40-/- or in CD40L-/- mice, whereas sequestration of parasitized red blood cells or polymorphonuclear leukocytes in alveolar capillaries was CD40-CD40L-independent. CD40 mRNA was increased in the brain and lung of infected mice whereas CD40L was increased in the lung. Tumor necrosis factor plasma levels were similarly increased in infected +/+ or CD40-/- mice. Expression of CD54 and its mRNA levels in the brain were moderately decreased in CD40-deficient mice. Thus the mortality associated with severe malaria requires CD40-CD40L interaction that contributes to the breakdown of the blood-brain barrier, macrophage sequestration, and platelet consumption.
Keywords AnimalsAntigens, CD40/genetics/physiologyBlood-Brain BarrierBrain/immunology/pathologyCD40 Ligand/genetics/physiologyGene Expression Regulation/immunologyIntercellular Adhesion Molecule-1/geneticsMacrophages/physiologyMalaria/blood/immunology/pathologyMiceMice, Inbred C57BLMice, KnockoutPlasmodium bergheiPlatelet CountRNA, Messenger/geneticsThrombocytopeniaTranscription, GeneticTumor Necrosis Factor-alpha/metabolism
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PMID: 11485931
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Article (Published version) (573 Kb) - public document Free access
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Research group Facteurs influençants le développement pulmonaire: étude translationnelle chez l'animal et l'homme (182)
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PIGUET, Pierre et al. Role of CD40-CVD40L in mouse severe malaria. In: American Journal of Pathology, 2001, vol. 159, n° 2, p. 733-42. https://archive-ouverte.unige.ch/unige:72629

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Deposited on : 2015-05-18

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