Role of the tumor necrosis factor receptor 2 (TNFR2) in cerebral malaria in mice.
- 2002-09-10
Published in:
- Laboratory investigation; a journal of technical methods and pathology. - 2002
Animals
Antigens, CD
Brain
CD4 Antigens
CD40 Antigens
CD40 Ligand
Capillary Permeability
Coma
Erythrocytes
Insulin
Macrophages
Malaria, Cerebral
Mice
Mice, Inbred C57BL
Mice, Inbred CBA
RNA, Messenger
Receptors, Tumor Necrosis Factor
Receptors, Tumor Necrosis Factor, Type I
Receptors, Tumor Necrosis Factor, Type II
Thrombocytopenia
English
Infection of susceptible mice with Plasmodium berghei Anka leads to a syndrome of severe or cerebral malaria. Tumor necrosis factor (TNF) contributes to this syndrome, apparently by acting on its receptor 2 (TNFR2) because TNFR1-/- are susceptible, whereas TNFR2-/- mice are resistant. In this work, we confirmed the essential role of the TNFR2 in cerebral malaria because 6 to 8 days after Plasmodium berghei Anka infection, hypothermia, coma, and death were observed in +/+ or TNFR1-/-, but never in TNFR2-/-, mice. TNF production, evaluated by the serum levels or the mRNA levels in the brain, spleen or lung, was similar in +/+, TNFR1-/-, or TNFR2-/- mice. Macrophage or parasitized red blood cell sequestration in brain or lung was similar in TNFR1-/- and TNFR2-/- mice. Accordingly, up-regulation of CD54 or CD40 in brain or lung was also similar in TNFR1-/- or TNFR2-/- mice. Platelet loss, manifested by thrombocytopenia and the presence of microparticles in plasma, was similar in TNFR1-/- or TNFR2-/- mice. Breakdown of the blood-brain barrier, detected by the diffusion of tracers, was attenuated in both TNFR1-/- and TNFR2-/-, compared with +/+, mice. Endothelial cells from brain capillaries, examined by transmission electron microscopy, were similar in infected TNFR1-/- or TNFR2-/- mice, whereas the basement membrane was enlarged in TNFR1-/- mice. Hypothermic mice were also hyperglycemic, and this was evident in +/+ and TNFR1-/-, but not in TNFR2-/-, mice. In addition, infected +/+ and TNFR1-/- mice became insulin resistant, while in contrast TNFR2-/- became extremely insulin sensitive. This study supports the possibility that coma and death are mediated not by cell sequestration or breakdown of vascular permeability, similar in TNFR1-/- or TNFR2-/- mice, but by metabolic disturbances selectively mediated by the TNFR2.
- Language
-
- English
- Open access status
- bronze
- Identifiers
-
- DOI 10.1097/01.lab.0000028822.94883.8a
- PMID 12218076
- Persistent URL
- https://sonar.ch/global/documents/152615
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