Role of TGF-beta and PGE2 in T cell responses during Plasmodium yoelii infection.
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.
Ocaña-Morgner
Carlos
C
New York University School of Medicine, Department of Medical Parasitology, New York, NY 10010, USA.
Wong
Kurt A
KA
Lega
Flavia
F
Dotor
Javier
J
Borras-Cuesta
Francisco
F
Rodriguez
Ana
A
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D000953:Antigens, Protozoan / Q000276:immunology; D039521:CD11c Antigen / Q000032:analysis; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D015232:Dinoprostone / Q000378:metabolism* / Q000502:physiology; D004912:Erythrocytes / Q000276:immunology / Q000469:parasitology; D016753:Interleukin-10 / Q000378:metabolism; D008288:Malaria / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000494:pharmacology; D010967:Plasmodium yoelii / Q000276:immunology*; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000378:metabolism; D018125:Receptors, Transforming Growth Factor beta; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000502:physiology; D014611:Vaccination
D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; C515370:CCR7 protein, human; D039521:CD11c Antigen; C515371:Ccr7 protein, mouse; D010446:Peptide Fragments; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D018125:Receptors, Transforming Growth Factor beta; C504795:TGF-beta1 type III receptor (730-743), human; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2