Biphasic response of dendritic cells to Plasmodium blood-stage infection in rodents. (a) Early on during infection, engagement of TLR-9 by hemozoin and interaction with infected red blood cells may result in dendritic-cell maturation. Mature dendritic cells present antigen to T cells and induce their activation. Activated T cells proliferate and migrate into primary B-cell follicles where they provide help for antibody production by B cells. (b) With increasing parasitemia, more and more myeloid dendritic cells in the spleen are paralyzed through ingestion of increasing amounts of hemozoin, with negative effects on downstream T-cell and B-cell responses.