The Journal of Experimental Medicine
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Published 20 January 2003. doi:10.1084/jem.20021072
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© Rockefeller University Press, 0022-1007/2003/1/143 $5.00
The Journal of Experimental Medicine, Volume 197, Number 2, 143-151

Malaria Blood Stage Suppression of Liver Stage Immunity by Dendritic Cells

Carlos Ocaña-Morgner1, Maria M. Mota2 and Ana Rodriguez1

1 Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, NY 10016
2 Department of Pathology, New York University School of Medicine, New York, NY 10016

Address correspondence to Ana Rodriguez, Department of Medical and Molecular Parasitology, 341 East 25th Street, New York, NY 10010. Phone: 212-263-6589; Fax: 212-263-8116; E-mail: rodria02{at}popmail.med.nyu.edu

Malaria starts with Plasmodium sporozoites infection of the host's liver, where development into blood stage parasites occurs. It is not clear why natural infections do not induce protection against the initial liver stage and generate low CD8+ T cell responses. Using a rodent malaria model, we show that Plasmodium blood stage infection suppresses CD8+ T cell immune responses that were induced against the initial liver stage. Blood stage Plasmodium affects dendritic cell (DC) functions, inhibiting maturation and the capacity to initiate immune responses and inverting the interleukin (IL)-12/IL-10 secretion pattern. The interaction of blood stage parasites with DCs induces the secretion of soluble factors that inhibit the activation of CD8+ T cells in vitro and the suppression of protective CD8+ T cell responses against the liver stage in vivo. We propose that blood stage infection induces DCs to suppress CD8+ T cell responses in natural malaria infections. This evasion mechanism leaves the host unprotected against reinfection by inhibiting the immune response against the initial liver stage of the disease.

Key Words: Plasmodium yoelii • sporozoites • CD8+ T cells • erythrocytes


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