16-16-dimethylprostaglandin-e2 and Malaria

During an acute blood-stage malaria infection, T cell responses to malaria and other bystander antigens are inhibited. Plasmodium infection induces strong cytokine responses that facilitate parasite clearance but may interfere with T cell functions, as some of the soluble immune mediators induced are also general inhibitors of T cell responses. Using a malaria mouse model, we have analyzed the cytokines produced by dendritic cells in response to P. yoelii infection that have potential T cell inhibitory activity. We found that during acute infection DC migrate to the spleen and secrete TGF-beta, prostaglandin E2 (PGE2) and IL-10. We have analyzed the role of these general T cell inhibitors in a particular T cell response of evident importance in malaria infections: the CD8+ T cells generated against the liver-stage of the disease. During blood-stage infection, inhibition of the activity of TGF-beta and PGE2 restores the CD8+ T cell responses generated by sporozoites, increasing protection against re-infection. Our findings suggest that the strong cytokine response induced by blood-stage P. yoelii infection affects host T cell responses, inhibiting protective CD8+ T cells against the liver-stage of the disease.

Topics: 16,16-Dimethylprostaglandin E2; Adoptive Transfer; Animals; Antibodies, Monoclonal; Antigens, Protozoan; CD11c Antigen; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Dendritic Cells; Dinoprostone; Erythrocytes; Interleukin-10; Malaria; Mice; Mice, Inbred BALB C; Peptide Fragments; Plasmodium yoelii; Receptors, CCR7; Receptors, Chemokine; Receptors, Transforming Growth Factor beta; Spleen; T-Lymphocytes; Transforming Growth Factor beta; Vaccination