Studying two complementary infection models to identify common mechanisms of intracellular parasite survival: The roles of Leishmania and Eimeria exo-kinases in subversion of host cell signalling - INRAE - Institut national de recherche pour l’agriculture, l’alimentation et l’environnement
Conference Poster Year : 2022

Studying two complementary infection models to identify common mechanisms of intracellular parasite survival: The roles of Leishmania and Eimeria exo-kinases in subversion of host cell signalling

Abstract

Upon infection, parasites secrete effector molecules particularly kinases, that modify their host cells to create a permissive environment. For instance, Leishmania secretes casein kinase 1.2 (L-CK1.2) into the host cell via exosomes. Previous studies in the lab demonstrated that L-CK1.2 interacts with and phosphorylates more than 200 host proteins in vitro. Moreover, L-CK1.2 when ectopically expressed alters the phosphorylation of 771 proteins in J774 macrophages. Pathway analysis of these host targets indicated that L-CK1.2 might have an impact on a multitude of host pathways, including a few known to be modified during Leishmania infection. During Eimeria tenella infection, rhoptry kinase 1 (EtROP1) inhibits host apoptosis by interacting with host p53. On comparison, it appears that these two exo-kinases from divergent parasites, impact similar host pathways such as apoptosis and cell cycle. Our hypothesis states that there might exist convergence in the host pathways modified by Leishmania and Eimeria. To investigate this hypothesis, we will perform phosphoproteomic and transcriptomic studies. For Leishmania, we have just established the first ever phosphoproteome for L donovani infected mouse BMDMs. We quantified about 12,000 phosphosites comparing infected versus uninfected, including 663 sites with a p-value below 0.05. In order to uncover L-CK1.2 specific effects, we also had infected cells treated or untreated with the L-CK1.2 inhibitor, D4476. Further analysis is ongoing. For E. tenella, chicken lung epithelial cells (CLEC213) were infected with either wild type or EtROP1 overexpressing parasites; the samples were collected and will soon be sent for transcriptomic analysis. Once we have the complete set, including the phosphoproteome for Eimeria-infected CLEC213 cells and the transcriptome for L. donovani-infected macrophages, we will then assess which pathways are similarly or differently modified during both infections and decipher their role by interfering with important genes of these pathways using CRISPR-Cas knockout, RNAi or overexpression.
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hal-04126119 , version 1 (13-06-2023)

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  • HAL Id : hal-04126119 , version 1

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Sharvani Shintre, Florent Dingli, Damarys Loew, Anne Silvestre, Najma Rachidi. Studying two complementary infection models to identify common mechanisms of intracellular parasite survival: The roles of Leishmania and Eimeria exo-kinases in subversion of host cell signalling. EMBO Workshop : New frontiers in host-parasite interactions, from cell to organism, Oct 2022, Six-Fours-Les-Plages, France. . ⟨hal-04126119⟩
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