Sending out an SOS: novel insights into a Toxoplasma effector protein

To survive within the host cell Toxoplasma secretes proteins from its specialized secretory organelles that interfere with host cell immune functions. A Toxoplasma rhoptry kinase named ROP16 promotes the phosphorylation of STAT6 (P-STAT6), a host transcriptional factor, leading to its activation and ultimately inducing M2-like polarization of macrophages. In addition, ROP16 was shown to be involved in enhanced cyst development.

We have previously shown that SOS1 knockout (KO) parasites induce a host transcriptional profile similar to that of ROP16 KO infected cells. SOS1 KO parasites were unable to sustain the P-STAT6 signal 24 h post-infection (hpi), revealing that, although SOS1 is not required to initially phosphorylate STAT6, it is necessary to sustain it. Similarly, SOS1 seems to be involved in maintaining cyst formation in vitro.

In the current study, we observe that maintenance of the P-STAT6 signal requires parasite invasion, and that co-infection with ROP16 KO and SOS1 KO parasites does not restore the P-STAT6 phenotype. This suggestes that invasion is required for signal maintenance and that both effectors must be present in the same parasite cell. Furthermore, increasing the parasite infection dose leads to a higher P-STAT6 signal at 24 hpi, indicating a dose-dependent effect.

Interestingly, SOS1 is conserved not only across Toxoplasma strains but also in other Apicomplexa species, such as Plasmodium falciparum and Cryptosporidium parvum, leading us to hypothesize that it may have a broader role in parasite biology. Ongoing work focuses on high-resolution spatial imaging of SOS1 KO parasites to unravel potential defects in rhoptry morphology and transcriptomic analysis of SOS1 KO and ROP16 KO infected cells to understand the wider function of SOS1. Future work also aims to investigate the role of SOS1 homologs in other Apicomplexa.

This work will deepen our understanding of Toxoplasma's mechanisms of immune system evasion while simultaneously providing insights into the overall biology of the parasite.