Figure 1.

Overview of a potential inflammatory cascade culminating in cerebral malaria pathology. Five consecutive events shape the outcome of a Plasmodium infection and contribute to cerebral malaria. During Plasmodium infection of the mammalian host, two consecutive parasite replication phases in the liver and red blood cells lead to distinct innate responses, which modulate downstream parasite/host cell interactions. Upon parasite accumulation in the microvasculature, endothelial cells become activated, leading to enhanced chemokine secretion, which in turn enhances leukocyte recruitment. Acute pathology is caused by permeabilization of the endothelial barrier. See Figures 2–6 for the central roles of chemokines and cytokines in the individual events.