Plasmodium parasite exploits host aquaporin-3 during liver stage malaria infection.

PLoS Pathog
Authors
Keywords
Abstract

Within the liver a single Plasmodium parasite transforms into thousands of blood-infective forms to cause malaria. Here, we use RNA-sequencing to identify host genes that are upregulated upon Plasmodium berghei infection of hepatocytes with the hypothesis that host pathways are hijacked to benefit parasite development. We found that expression of aquaporin-3 (AQP3), a water and glycerol channel, is significantly induced in Plasmodium-infected hepatocytes compared to uninfected cells. This aquaglyceroporin localizes to the parasitophorous vacuole membrane, the compartmental interface between the host and pathogen, with a temporal pattern that correlates with the parasite's expansion in the liver. Depletion or elimination of host AQP3 expression significantly reduces P. berghei parasite burden during the liver stage and chemical disruption by a known AQP3 inhibitor, auphen, reduces P. falciparum asexual blood stage and P. berghei liver stage parasite load. Further use of this inhibitor as a chemical probe suggests that AQP3-mediated nutrient transport is an important function for parasite development. This study reveals a previously unknown potential route for host-dependent nutrient acquisition by Plasmodium which was discovered by mapping the transcriptional changes that occur in hepatocytes throughout P. berghei infection. The dataset reported may be leveraged to identify additional host factors that are essential for Plasmodium liver stage infection and highlights Plasmodium's dependence on host factors within hepatocytes.

Year of Publication
2018
Journal
PLoS Pathog
Volume
14
Issue
5
Pages
e1007057
Date Published
2018 05
ISSN
1553-7374
DOI
10.1371/journal.ppat.1007057
PubMed ID
29775485
PubMed Central ID
PMC5979039
Links
Grant list
DP2 AI138239 / AI / NIAID NIH HHS / United States
S10 OD018164 / OD / NIH HHS / United States
1DP2AI138239 / NH / NIH HHS / United States