**9. Apoptosis inhibition in** *Plasmodium* **spp. infection**

In the mammalian host, *Plasmodium* parasites infect primarily hepatocytes and erythrocytes, and modulation of apoptosis by this parasite in both host cell types has been found to be crucial during infection. After transmission by the *Anopheles* mosquito, *Plasmodium* sporozoites are rapidly transported to the liver, where they invade and develop within hepatocytes before reaching erythrocytes [168]. In the liver, sporozoites transmigrate through the cytosol of multiple hepatocytes, causing wounding in the traversed cells with the release of the hepatocyte growth factor (HGF), which helps the parasite to reach a final hepatocyte in which it will reside and multiply [158, 169, 170]. It has been proposed that HGF binds to the c-mesenchymal-epithelial transition factor (c-Met) located on the surface of hepatocytes, a process that leads to PI3-K activation and a further protection of these cells from apoptosis [171, 172]. Albeit PI3-K activation trough HGF/c-Met signaling has been proposed to protect hepatocytes from apoptosis during early liver stages of infection with *Plasmodium*, other data suggest that PI3-K activation is not required to maintain this antiapoptotic state [173].

During the blood stage of infection with *Plasmodium*, in which merozoites invade erythrocytes, multiple changes are induced in the host cell by the parasite in order to satisfy its nutritional requirements [164]. One of these changes is the activation of Ca2+ permeable channels in the plasmatic membrane of erythrocytes and the posterior entry of Ca2+ into these cells. An increase in the intracellular concentration of Ca2+ in erythrocytes has been demonstrated to induce a type of programmed cell death called eryptosis, which is characterized by cell shrinkage, cell membrane blebbing, and exposure of phosphatidyl serine, resembling apoptosis [174]. Due that infection with *Plasmodium* leads to the entry of Ca2+ into the erythrocytes and that the increment of the concentration of this ion stimulates eryptosis, it has been shown that *Plasmodium* can delay the execution of this programmed cell death mechanism by sequestering free Ca2+ ions present in the cytosol of erythrocytes [175].
