In falciparum malaria, the scavenger receptor CD36 plays multiple roles: (i) mediates the sequestration of parasites in the microvascular endothelia through the adherence of parasite-infected erythrocytes, (ii) supports phagocytic clearance of parasites by macrophages, and (iii) modulates immune responses to parasites. While the function of CD36 in the parasite sequestration and clearance has been extensively studied, its role in malaria immunity remains poorly understood. We studied the role of CD36 in cytokine responses to malaria parasite, Plasmodiun falciparum, by DCs and in DC function. Blocking of CD36 with anti-CD36 antibodies resulted in the substantial decrease in the levels of infected erythrocyte internalization and pro-inflammatory cytokine responses by DCs. Consistent with these results, DCs deficient in CD36 internalized lower levels of infected erythrocytes and produced decreased levels of pro-inflammatory cytokines. The observed CD36-depedent internalization and cytokine responses by DCs are evident at relatively low doses of infected erythrocytes; at higher doses, the contribution of CD36 become masked due to the increased rate of infected erythrocyte uptake by various other receptor-mediated phagocytosis. Furthermore, IFN-γ production by NK and T cells incubated with IRBC-internalized DCs was dependent on CD36. Overall, our data demonstrate that CD36 plays a critical role in the development of immunity to malaria.
- Copyright © 2013 by The American Association of Immunologists, Inc.