Abstract
SummaryOrganisms have evolved numerous strategies to control infection by an array of intracellular pathogens. One cell autonomous pathogen control strategy is global inhibition of protein synthesis via stress granule (SG) formation. SGs are induced by stressful stimuli such as oxidative stress and nutrient deprivation, and are known to counteract both viral and bacterial infections. Pathogens, in turn, may actively block an infected cell's ability to form SGs. In vitro and in vivo, many liver stage malaria parasites are eliminated during development. We show here that SG formation is not amongst the strategies used for elimination of parasites from hepatocytes. Neither cell traversal, sporozoite invasion, nor rapid parasite growth leads to the formation of SGs. Furthermore, Plasmodium berghei infection does not compromise the ability of infected cells to assemble SGs in response to oxidative or nutritional stress. Plasmodium infection is therefore not detected by hepatocytes as a strong stressor necessitating global translational repression in response, highlighting the idea that Plasmodium has evolved strategies to ensure its remarkable growth in the hepatocyte while maintaining host cell homeostasis.
Highlights
Plasmodium parasites are Apicomplexan protozoans with a complex lifecycle encompassing motile, non-replicative and sessile, replicative forms in both the mosquito and mammalian host
We show here that stress granule (SG) formation is not amongst the strategies used for elimination of parasites from hepatocytes
Plasmodium berghei infection does not compromise the ability of infected cells to assemble SGs in response to oxidative or nutritional stress
Summary
Plasmodium parasites are Apicomplexan protozoans with a complex lifecycle encompassing motile, non-replicative and sessile, replicative forms in both the mosquito and mammalian host. During the initial stage of infection in the mammalian host, Plasmodium sporozoites are transferred from an infected mosquito into the dermis Many of these motile sporozoites enter the circulatory system, and after arresting in the liver sinusoids, traverse several cells, before invading a final hepatocyte, and there establishing residence inside a parasitophorous vacuole. Inside this vacuole, the parasite undergoes a remarkable expansion, generating thousands of progeny in as little as two days during this clinically silent phase of infection. Whether or not the host cell can recognize the parasite via pathogen-associated molecular patterns (PAMPs) (Liehl and Mota, 2012), the infection process could induce cellular stress responses in the host cell during the invasion process itself, which ends in the internalization of a sizeable (roughly 10 mm long, 2 mm in diameter) object into the cell cytoplasm, or during the remarkable EEF growth that occurs after the onset of DNA replication (Prudencio et al, 2006)
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