Host ER stress during malaria parasite infection

After transmission by Anopheles mosquitoes, malaria parasite sporozoites target the liver, where they infect hepatocytes and multiply thousands of times. The release of new parasites into the blood stream then initiates symptomatic red blood cell infection. Although successful replication within hepatocytes is critical for host infection, little is known about parasite–hepatocyte interactions that ensure parasite survival and development. In this issue of EMBO R eports , the Mota group describes a beneficial role of the host ER stress pathway for P lasmodium survival in infected hepatocytes [1][Inácio P, 2015]. They demonstrate that proteins and transcripts that act in the u nfolded p rotein r esponse ( UPR ) are elevated in hepatocytes in response to infection. Reversing these perturbations by eliminating the splicing of XBP 1 or knockdown of CREBH is detrimental to parasite development. These findings are of significant interest in light of recent findings that elucidate other aspects of liver‐stage parasite–hepatocyte interactions and raise new, intriguing questions for the field (Fig 1).