Direct activation of dendritic cells by the malaria parasite, Plasmodium chabaudi chabaudi

A primary infection of mice with Plasmodium chabaudi chabaudi (AS) is chara cterized by a rapid and marked inflammatory response. Typically, IL-12, TNF -alpha and IFN-gamma are produced in the spleen, and are transiently presen t in plasma. The cells involved in this early response are unknown. Here we show that dendritic cells derived from GM-CSF-stimulated mouse bone marrow cultures produce TNF-a within 30 min of exposure to P.c.chabaudi schizonts . IL-6, IL-12p40 and p70 follow this. The production of these cytokines was not dependent on the presence of T cells or NK cells and did not require C D40. Incubation of dendritic cells with Pc.chabaudi schizonts also resulted in up-regulation of MHC class II, CD40 and CD86 but not CD80. In contrast to some strains of the human parasite, P falciparum, Pc. chabaudi (AS) did not inhibit the up-regulation of MHC class II, CD86 or CD40 induced by LIPS . Therefore, the erythrocytic stages of P.c.chabaudi are able to activate d endritic cells directly. The consequences of such an interaction could be r apid activation of TH1 cells and induction of immunity, and in the event of a large response also induction of TNF-alpha associated pathology.