Author: jsaeij

In a review in Trends in Parasitology, the lab synthesizes how human Vγ9Vδ2 T cells detect intracellular parasites. These cells recognize phosphoantigens that accumulate inside infected cells, through cooperation of the butyrophilins BTN3A1 and BTN2A1, and respond with rapid cytotoxicity and interferon-γ.

Toxoplasma depends on lipids taken from its host cell to expand its vacuole and replicate. In Cell Reports we identify TgSEC14-LTP1, a previously uncharacterized dense granule protein with a divergent SEC14/CRAL-TRIO domain that is secreted into the vacuole lumen and is essential for replication.

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…

A genome-wide CRISPR screen in lipid-rich versus lipid-poor culture conditions, published in Nature Communications, identified the dense granule protein GRA38 as a regulator of parasite fitness that depends on lipid availability.

Toxoplasma spreads through the body by riding inside infected immune cells, which it turns hypermotile. We previously showed that this depends on the secreted effector TgWIP. In mBio we now show that TgWIP binds the host adaptor proteins Nck1 and Grb2 through two proline-rich regions, and the WAVE regulatory complex through a WIRS motif.

Fatal infections with the rare COUG strain of Toxoplasma gondii have emerged in southern sea otters off the California coast. This PLoS One study, led by Karen Shapiro’s lab at UC Davis with our lab as collaborators, describes six additional deaths, most with the severe, widespread steatitis that defined the first cases.

The major surface antigen SAG1 was a consistent hit in CRISPR screens for parasite genes needed in interferon-γ-stimulated cells. In Infection and Immunity we show with a SAG1 knockout that the protein is important for fitness specifically under interferon-γ.