Role of CD40-CVD40L in mouse severe malaria

Am J Pathol. 2001 Aug;159(2):733-42. doi: 10.1016/s0002-9440(10)61744-0.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier
  • Brain / immunology
  • Brain / pathology
  • CD40 Antigens / genetics
  • CD40 Antigens / physiology*
  • CD40 Ligand / genetics
  • CD40 Ligand / physiology*
  • Gene Expression Regulation / immunology
  • Intercellular Adhesion Molecule-1 / genetics
  • Macrophages / physiology
  • Malaria / blood
  • Malaria / immunology*
  • Malaria / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasmodium berghei*
  • Platelet Count
  • RNA, Messenger / genetics
  • Thrombocytopenia
  • Transcription, Genetic
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • CD40 Antigens
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • CD40 Ligand