title: Susceptibility to Plasmodium yoelii preerythrocytic infection in BALB/c substrains is determined at the point of hepatocyte invasion.
abstract: 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.
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Kaushansky
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA.
authors.forename: Laura S
authors.initials: LS
authors.lastname: Austin
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA.
authors.forename: Sebastian A
authors.initials: SA
authors.lastname: Mikolajczak
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA.
authors.forename: Fang Y
authors.initials: FY
authors.lastname: Lo
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Miller
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA.
authors.forename: Alyse N
authors.initials: AN
authors.lastname: Douglass
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA.
authors.forename: Nadia
authors.initials: N
authors.lastname: Arang
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA.
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Vaughan
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA.
authors.forename: Malcolm J
authors.initials: MJ
authors.lastname: Gardner
authors.affiliation: Seattle Biomedical Research Institute, Seattle, Washington, USA Department of Global Health, University of Washington, Seattle, Washington, USA stefan.kappe@seattlebiomed.org.
authors.forename: Stefan H I
authors.initials: SH
authors.lastname: Kappe
mesh_terms: D000818:Animals; D004198:Disease Susceptibility; D004705:Endocytosis; D005260:Female; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000469:parasitology*; D008288:Malaria / Q000276:immunology* / Q000469:parasitology*; D008807:Mice, Inbred BALB C; D010967:Plasmodium yoelii / Q000502:physiology*