A new Toxoplasma rhoptry protein is a major virulence factor that prevents inflammatory host cell death

Programmed-cell death is an antimicrobial mechanism of defense that promotes rapid clearance of intracellular pathogens. Toxoplasma counteracts host immune defenses by secreting effector proteins into host cells; however, how the parasite evades inflammatory cell death and the effectors involved remain poorly characterized. We identified a new Toxoplasma virulence factor that ensures parasite survival by blocking host cell death. RNA-Seq analysis revealed that this rhoptry protein acts as a repressor of host pro-inflammatory responses. THP1 human monocytes infected with a mutant Toxoplasma strain, showed increased nuclear translocation of NF-kB p65, IL-1β and LDH release, compared to infection with wild type or complemented parasites. Moreover, mutant parasites were dramatically impaired in virulence in mice also preventing NF-κB signalling and lytic cell death in BMDM. These findings unravel the role of a major virulence factor of Toxoplasma, supressing inflammatory cell death as a strategy to evade parasite clearance.