title: Selection and refinement: the malaria parasite's infection and exploitation of host hepatocytes.
abstract: Plasmodium parasites belong to the Apicomplexan phylum, which consists mostly of obligate intracellular pathogens that vary dramatically in host cell tropism. Plasmodium sporozoites are highly hepatophilic. The specific molecular mechanisms, which facilitate sporozoite selection and successful infection of hepatocytes, remain poorly defined. Here, we discuss the parasite and host factors which are critical to hepatocyte infection. We derive a model where sporozoites initially select host cells that constitute a permissive environment and then further refine the chosen hepatocyte during liver stage development, ensuring life cycle progression. While many unknowns of pre-erythrocytic infection remain, advancing models and technologies that enable analysis of human malaria parasites and of single infected cells will catalyze a comprehensive understanding of the interaction between the malaria parasite and its hepatocyte host.
authors.affiliation: Center for Infectious Disease Research, Formerly Seattle Biomedical Research Institute, 307 Westlake Ave. N, #500, Seattle, WA 98109, United States. Electronic address: alexis.kaushansky@cidresearch.org.
authors.forename: Alexis
authors.initials: A
authors.lastname: Kaushansky
authors.affiliation: Center for Infectious Disease Research, Formerly Seattle Biomedical Research Institute, 307 Westlake Ave. N, #500, Seattle, WA 98109, United States; Department of Global Health, University of Washington, Seattle, WA, United States. Electronic address: stefan.kappe@cidresearch.org.
authors.forename: Stefan Hi
authors.initials: SH
authors.lastname: Kappe
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D022781:Hepatocytes / Q000469:parasitology*; D054884:Host-Pathogen Interactions; D006801:Humans; D008954:Models, Biological; D010274:Parasitology / Q000379:methods; D010961:Plasmodium / Q000502:physiology*