Toxoplasma gondii ROP18I inhibits host innate immunity through cGAS-STING signaling

Toxoplasma gondii is an opportunistic protozoan, which widely infects humans and other warm-blooded animals. The type I interferon (IFN) such as IFN-alpha/beta is involved in cGAS-STING signaling to resist T. gondii infection. We found in RAW264.7 cells, that T. gondii virulence factor TgROP18(I), inhibited IFN-beta production through interacting with interferon regulatory factor 3 (IRF3). Besides, TgROP18(I) interacted with p62 and Tumor Necrotic Factor Receptor Associated Factor 6 (TRAF6), which resulted in the inhibition of TRAF6-p62 interaction, and phosphorylation of p62. Furthermore, TgROP18 1 restricted the recruitment of ubiquitin. p62 and microtubule-associated protein light chain 3 (LC3) to the parasitophorous vacuole membrane (PVM) in IFN-gamma-stimulated murine cell line L929 cells. In IFN-gamma-stimulated human cells, TgROP18(I) restricted the decoration of PVM with ubiquitin, p62, and LC3, and bound with TRAF2, TRAF6, and p62, respectively. As a result, TgROP18(I) led to a successful parasitic replication in murine and human cells. Collectively, our study revealed the function of TgROP18(I) in suppressing host type I interferon responses in T. gondii infection for parasitic immune escape.

Automated summary

TgROP18(I) inhibits type I interferon responses to facilitate parasitic replication in various host cells.