Host cell-specific metabolism of linoleic acid controls Toxoplasma gondii growth in cell culture

bioRxiv [Preprint]. 2024 Mar 25:2024.03.22.586332. doi: 10.1101/2024.03.22.586332.

Abstract

The obligate intracellular parasite Toxoplasma gondii can infect and replicate in any warm-blooded cell tested to date, but much of our knowledge about T. gondii cell biology comes from just one host cell type: human foreskin fibroblasts (HFFs). To expand our knowledge of host-parasite lipid interactions, we studied T. gondii in intestinal epithelial cells, the first site of host-parasite contact following oral infection and the exclusive site of parasite sexual development in feline hosts. We found that highly metabolic Caco-2 cells are permissive to T. gondii growth even when treated with high levels of linoleic acid (LA), a polyunsaturated fatty acid (PUFA) that kills parasites in HFFs. Caco-2 cells appear to sequester LA away from the parasite, preventing membrane disruptions and lipotoxicity that characterize LA-induced parasite death in HFFs. Our work is an important step toward understanding host-parasite interactions in feline intestinal epithelial cells, an understudied but important cell type in the T. gondii life cycle.

Keywords: Toxoplasma gondii; enterocyte; linoleic acid; lipid droplet; lipotoxicity; polyunsaturated fatty acid.

Publication types

  • Preprint