Intracellular Promote Invasive Cell Motility through Kinase Regulation of the Host Actin Cytoskeleton

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The protozoan parasite Theileria annulata causes the often fatal leukoproliferative disorder Tropical Theileriosis in their ruminant host animals, which is the result of widespread dissemination and proliferation of cytokine secreting, parasite-infected cells. This host cell behavior is induced by and dependent on the intracellular presence of the parasite and is reminiscent of metastatic dissemination of human cancer cells. We investigated how the intracellular parasite modulates cell motility and invasiveness, to better understand the pathogenesis of Tropical Theileriosis and to reveal conserved mechanisms of eukaryotic cell motility regulation. We found that the parasite drives host cell motility and invasiveness through the induction and activation of the host cell protein MAP4K4. We show that MAP4K4 induction is driven by the inflammatory cytokine TNFα and causes dynamic changes in the cytoskeleton of the host cell that facilitate cell motility. Thus, our findings reveal how the intracellular Theileria parasite can influence morphology and behavior of its host cell in a way that suits its propagation and highlight a novel function of chronic TNFα production for the pathogenesis of Tropical Theileriosis. Furthermore, our study revealed a novel aspect of inflammatory cytokine action, namely cell mobilization through the induction of the evolutionary conserved protein kinase MAP4K4.

Vyšlo v časopise: Intracellular Promote Invasive Cell Motility through Kinase Regulation of the Host Actin Cytoskeleton. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1004003
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004003

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