Group 1 metabotropic glutamate receptor expression defines a T cell memory population during chronic Toxoplasma infection that enhances IFN-gamma and perforin production in the CNS

Within the brain, a pro-inflammatory response is essential to prevent clinical disease due to Toxoplasma gondii reactivation. Infection in the immunocompromised leads to lethal Toxoplasmic encephalitis while in the immunocompetent, there is persistent low-grade inflammation which is devoid of clinical symptoms. T cells are the dominant immune cell that prevent clinical disease, and this is mediated through the secretion of effector molecules such as perforins and IFNγ. However, other extrinsic signals that promote protection and the formation of memory T cells within tissue are poorly understood. During chronic infection, there is an increase in extracellular glutamate that, due to its function as an excitatory neurotransmitter, is normally tightly controlled in the brain. To investigate glutamate’s influence of CD8 T cells, single cell RNA-sequencing (scRNA-seq) was performed on brain CD8 T cells that were cell-sorted for CD3+CD8+mGluR1-mGluR5- or CD3+CD8+mGluR1+mGluR5+ expression. In addition, we also sorted on splenic CD8 T cells isolated from 3wpi mice with the aforementioned genotype for comparative analysis We sequenced 27497 sorted CD8 T cells from Toxoplasma-infected brain (8904) or spleen (18593), 3-weeks post infection (wpi). This dataset is composed of one sorted population of CD3+CD8+mGluR1-mGluR5- brain T cells (7676), and three replicates of CD3+CD8+mGluR1+mGluR5+ brain T cells (324, 570, 334). Additionally, splenic T cells were also sorted for CD3+CD8+mGluR1-mGluR5- (16091) or CD3+CD8+mGluR1+mGluR5+ (2502) expression.