Toxoplasma gondii ROP18 I inhibits host innate immunity through cGAS‐STING signaling

Abstract Toxoplasma gondii is an opportunistic protozoan, which widely infects humans and other warm‐blooded animals. The type I interferon (IFN) such as IFN‐α/β is involved in cGAS‐STING signaling to resist T . gondii infection. We found in RAW264.7 cells, that T . gondii virulence factor Tg ROP18 I , inhibited IFN‐β production through interacting with interferon regulatory factor 3 (IRF3). Besides, Tg ROP18 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, Tg ROP18 I restricted the recruitment of ubiquitin, p62 and microtubule‐associated protein light chain 3 (LC3) to the parasitophorous vacuole membrane (PVM) in IFN‐γ‐stimulated murine cell line L929 cells. In IFN‐γ‐stimulated human cells, Tg ROP18 I restricted the decoration of PVM with ubiquitin, p62, and LC3, and bound with TRAF2, TRAF6, and p62, respectively. As a result, Tg ROP18 I led to a successful parasitic replication in murine and human cells. Collectively, our study revealed the function of Tg ROP18 I in suppressing host type I interferon responses in T . gondii infection for parasitic immune escape.