Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue

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Abstract
The protozoon Toxoplasma gondii causes intracellular infections with extraordinary differences in disease severity, ranging from inevitable death to a mild chronic infection. The reason for this variation has been something of a mystery, but an enzyme that could be responsible has now been identified. Toxoplasma injects a protein kinase into the host cell that is rapidly transported to the nucleus where it dramatically alters host gene expression, including genes that determine the host response to infection. Different Toxoplasma strains have different versions of this protein, and this could explain the wide variations in pathogenicity. Toxoplasma gondii causes intracellular infections with disease severity that varies depending on the pathogen strain. A potential mechanism has now been elucidated, whereby the presence of a putative kinase in certain strains results in the activation of distinct host signalling pathways. Toxoplasma gondii, an obligate intracellular parasite of the phylum Apicomplexa, can cause severe disease in humans with an immature or suppressed immune system. The outcome of Toxoplasma infection is highly dependent on the strain type, as are many of its in vitro growth properties1. Here we use genetic crosses between type II and III lines to show that strain-specific differences in the modulation of host cell transcription are mediated by a putative protein kinase, ROP16. Upon invasion by the parasite, this polymorphic protein is released from the apical organelles known as rhoptries and injected into the host cell, where it ultimately affects the activation of signal transducer and activator of transcription (STAT) signalling pathways and consequent downstream effects on a key host cytokine, interleukin (IL)-12. Our findings provide a new mechanism for how an intracellular eukaryotic pathogen can interact with its host and reveal important differences in how different Toxoplasma lineages have evolved to exploit this interaction.