Document Type
Article
Publication Date
3-19-2019
Publication Title
Cell Rep
Keywords
Animals; Cell Line; Hepatocytes; Humans; Malaria; Mice; Mice, Inbred BALB C; Phosphorylation; Plasmodium yoelii; Ribosomal Protein S6; Toxoplasma; Toxoplasmosis
Abstract
Plasmodium parasites are highly selective when infecting hepatocytes and induce many changes within the host cell upon infection. While several host cell factors have been identified that are important for liver infection, our understanding of what facilitates the maintenance of infection remains incomplete. Here, we describe a role for phosphorylated ribosomal protein S6 (Ser235/236) (p-RPS6) in Plasmodium yoelii-infected hepatocytes. Blocking RPS6 phosphorylation prior to infection decreases the number of liver stage parasites within 24 h. Infected hepatocytes exhibit elevated levels of p-RPS6 while simultaneously abrogating the induction of phosphorylation of RPS6 in response to insulin stimulation. This is in contrast with the regulation of p-RPS6 by Toxoplasma gondii, which elevates levels of p-RPS6 after infection but does not alter the response to insulin. Our data support a model in which RPS6 phosphorylation is uncoupled from canonical regulators in Plasmodium-infected hepatocytes and is relied on by the parasite to maintain infection.
Clinical Institute
Digestive Health
Department
Institute for Systems Biology
Department
Infectious Diseases
Recommended Citation
Glennon, Elizabeth K K; Austin, Laura S; Arang, Nadia; Kain, Heather S; Mast, Fred D; Vijayan, Kamalakannan; Aitchison, John D; Kappe, Stefan H I; and Kaushansky, Alexis, "Alterations in Phosphorylation of Hepatocyte Ribosomal Protein S6 Control Plasmodium Liver Stage Infection." (2019). Articles, Abstracts, and Reports. 3273.
https://digitalcommons.providence.org/publications/3273
