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

Nature advance online publication 20 December 2006 doi:10.1038/nature05395; Received 13 July 2006; Accepted 1 November 2006; Published online 20 December 2006

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

J. P. J. Saeij1,3, S. Coller1,3, J. P. Boyle1, M. E. Jerome2, M. W. White2 and J. C. Boothroyd1

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.

http://www.nature.com/nature/journal/vaop/ncurrent/pdf/nature05395.pdf