Susceptibility to Plasmodium yoelii preerythrocytic infection in BALB/c substrains is determined at the point of hepatocyte invasion

After transmission by Anopheles mosquitoes, Plasmodium sporozoites travel to the liver, infect hepatocytes, and rapidly develop as intrahepatocytic liver stages (LS). Rodent models of malaria exhibit large differences in the magnitude of liver infection, both between parasite species and between str...

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Bibliographic Details
Published in:Infection and immunity 2015-01, Vol.83 (1), p.39-47
Main Authors: Kaushansky, Alexis, Austin, Laura S, Mikolajczak, Sebastian A, Lo, Fang Y, Miller, Jessica L, Douglass, Alyse N, Arang, Nadia, Vaughan, Ashley M, Gardner, Malcolm J, Kappe, Stefan H I
Format: Article
Language:English
Subjects:
Animals
Anopheles
Cellular Microbiology: Pathogen-Host Cell Molecular Interactions
Disease Susceptibility
Endocytosis
Female
Gene Expression Profiling
Hepatocytes - parasitology
Malaria - immunology
Malaria - parasitology
Mice, Inbred BALB C
Plasmodium yoelii
Plasmodium yoelii - physiology
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Summary:After transmission by Anopheles mosquitoes, Plasmodium sporozoites travel to the liver, infect hepatocytes, and rapidly develop as intrahepatocytic liver stages (LS). Rodent models of malaria exhibit large differences in the magnitude of liver infection, both between parasite species and between strains of mice. This has been mainly attributed to differences in innate immune responses and parasite infectivity. Here, we report that BALB/cByJ mice are more susceptible to Plasmodium yoelii preerythrocytic infection than BALB/cJ mice. This difference occurs at the level of early hepatocyte infection, but expression levels of reported host factors that are involved in infection do not correlate with susceptibility. Interestingly, BALB/cByJ hepatocytes are more frequently polyploid; thus, their susceptibility converges on the previously observed preference of sporozoites to infect polyploid hepatocytes. Gene expression analysis demonstrates hepatocyte-specific differences in mRNA abundance for numerous genes between BALB/cByJ and BALB/cJ mice, some of which encode hepatocyte surface molecules. These data suggest that a yet-unknown receptor for sporozoite infection, present at elevated levels on BALB/cByJ hepatocytes and also polyploid hepatocytes, might facilitate Plasmodium liver infection.
ISSN:0019-9567
1098-5522
DOI:10.1128/iai.02230-14