Scientific article
Open access

Role of CD40-CVD40L in mouse severe malaria

Published inThe American journal of pathology, vol. 159, no. 2, p. 733-742
Publication date2001

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.

  • Animals
  • Antigens, CD40/genetics/physiology
  • Blood-Brain Barrier
  • Brain/immunology/pathology
  • CD40 Ligand/genetics/physiology
  • Gene Expression Regulation/immunology
  • Intercellular Adhesion Molecule-1/genetics
  • Macrophages/physiology
  • Malaria/blood/immunology/pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasmodium berghei
  • Platelet Count
  • RNA, Messenger/genetics
  • Thrombocytopenia
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha/metabolism
Citation (ISO format)
PIGUET, Pierre et al. Role of CD40-CVD40L in mouse severe malaria. In: The American journal of pathology, 2001, vol. 159, n° 2, p. 733–742. doi: 10.1016/S0002-9440(10)61744-0
Main files (1)
Article (Published version)
ISSN of the journal0002-9440

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