Figure 2.

Liver stage development. Graphic representation of liver stage maturation that leads to the formation of exoerythrocytic merozoites. (A) The tubulovesicular network (TVN) (blue)—membrane-bound extensions and whorls that emanate from the parasitophorous vacuole membrane (PVM)—interacts with the hepatocyte’s autophagosomes (which express Atg8/LC3) likely for nutrient uptake. Parasite proteins expressed on the PVM/TVN include IBIS1, EXP1, UIS4, and UIS3, which has been shown to interact with host L-FABP. The parasite plasma membrane (PPM)-associated protein B9 is known to be important for liver stage development. (B) As the liver stage parasite matures, multiple invaginations of the PPM occur (cytomere formation), and this is accompanied by the expression of MSP1 and ZIPCO. Additionally, LISP1 and LISP2 expression occur on the PVM. (C) Toward the end of liver stage development, individual exoerythrocytic merozoites begin to form, the PVM breaks down (a process that relies on LISP1), and LISP2 is released into the host hepatocyte. (D) Merosomes, merozoites surrounded by hepatocyte plasma membrane, are released into the bloodstream through the liver sinusoid, which is demarcated by epithelial cells (red) and liver resident macrophages, the Kupffer cells (yellow).