The Nrf2 pathway is required for intracellular replication of Toxoplasma gondii in activated macrophages.

Reactive oxygen species (ROS) produced by oxidases and nonenzymatic sources are important for host defence against intracellular pathogens. In this study, we knocked out the Nrf2 gene in RAW264.7 cells using the CRISPR/Cas9 system and investigated the antioxidant effects of the Nrf2 pathway in the cells stimulated by IFN-γ and TNF-α. The results indicated that the Nrf2 signalling pathway is necessary for maintaining redox homeostasis in activated RAW264.7 cells. Inactivation of Nrf2 impaired parasite growth. We also found that p62 contributes to Nrf2-mediated pathways involved in T gondii infection. These findings suggest that the Nrf2/Keap1 pathway may be targeted to prevent and treat toxoplasmosis.