Immune Evasion Strategies of Pre-Erythrocytic Malaria Parasites

Figure 2

The manipulation of hepatocytes by sporozoites. Sporozoites transmigrate several hepatocytes prior to settling in a final cell. Transmigrated hepatocytes release HGF, which binds to the C-MET receptor, making the hepatocyte susceptible to infection and resistant to apoptosis by upregulation of MAPK, and Akt (left). The interaction of CSP with high levels of HSPGs triggers the cleavage of CSP and encapsulation of sporozoites in parasitophorous vacuoles. Cleaved CSP escapes from the parasitophorous vacuole into the cytoplasm, where it inhibits the NF-κB activation and host protein synthesis. Sporozoite invasion upregulates mTOR and downregulates p53, and Bcl-2 which block autophagy, cell cycle progression and Apoptosis, respectively (middle). To avoid destruction by KCs and DCs during release from hepatocytes, merozoites bud from the hepatocytes in merosomes, which are covered with host cell-derived membranes, and PS exposure on the outer leaflet of the dying hepatocytes is blocked (right).