Toxoplasma co-opts host gene expression by injection of a polymorphic kinase homologue.
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 properties. 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.
Saeij
J P J
JP
Department of Microbiology and Immunology, Fairchild Building D305, 300 Pasteur Drive, Stanford University School of Medicine, Stanford, California 94305-5124, USA.
Coller
S
S
Boyle
J P
JP
Jerome
M E
ME
White
M W
MW
Boothroyd
J C
JC
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism / Q000469:parasitology; D003433:Crosses, Genetic; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism; D008297:Male; D010770:Phosphotransferases / Q000378:metabolism*; D015800:Protozoan Proteins / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014122:Toxoplasma / Q000145:classification / Q000201:enzymology* / Q000235:genetics / Q000502:physiology*; D014123:Toxoplasmosis / Q000235:genetics* / Q000469:parasitology*; D014158:Transcription, Genetic / Q000235:genetics
D015800:Protozoan Proteins; D050796:STAT3 Transcription Factor; D050800:STAT6 Transcription Factor; D018664:Interleukin-12; D010770:Phosphotransferases