Mice detect Toxoplasma through TLR11/12 and IRG proteins that humans lack, so how humans first sense the parasite has been unclear. Using primary human blood cells, we show in PLoS Pathogens that Vγ9Vδ2 T cells are activated by Toxoplasma-infected cells in a BTN3A1-dependent way, secrete interferon-γ and TNFα, and boost interferon-γ production by NK cells via TNFα and IL-12.
Active invasion is required, and infection raises host phosphoantigen levels through the mevalonate pathway: blocking that pathway blunts the cytokine response. Vγ9Vδ2 T cells thus bridge innate and adaptive immunity in the early human response to the parasite.
Read the paper: The early human interferon gamma response to Toxoplasma gondii is driven by Vγ9Vδ2 T-cell sensing of host phosphoantigens and subsequent NK-cell activation. PLoS Pathog 2025.