A Plasmodium yoelii soluble factor inhibits the phenotypic maturation of dendritic cells

Background: Infection with the protozoan parasite Plasmodium is the cause of malaria. Plasmodium infects host erythrocytes causing the pathology of the disease. Plasmodium-infected erythrocytes can modulate the maturation of dendritic cells (DCs) and alter their capacity to activate T cells. Methods: Mice infected with Plasmodium yoelii and isolated P. yoelii-infected erythrocytes were used to study their effect on the maturation of mouse dendritic cells. Results: DCs are not able to mature in response to LPS injection during the late stage of P. yoelii infection in mice, indicating impaired functionality of these cells in vivo. P. yoelii-infected erythrocytes inhibit the maturation of DCs in vitro in a dose-dependent manner, which is consistent with the inhibition found during late infection when parasite burden is highest. The inhibition of DC maturation and the cytokine secretion profile of DCs are modulated by soluble factors released by P. yoelii-infected erythrocytes. A small, heat-stable, non-hydrophobic molecule of P. yoelii-infected erythrocytes rapidly inhibits the LPS induced phenotypic maturation of DCs in a reversible manner. Conclusion: These findings add evidence to the malaria associated immune suppression in vivo and in vitro and provide insight into the nature and mechanism of the Plasmodium factor(s) responsible for altering DC functions.