Temporal RNA-seq analysis reveals previously uncharacterized B cell infiltration during late chronic cerebral toxoplasmosis

Chronic toxoplasmosis begins when tachyzoites cross the blood-brain barrier and enter the Central Nervous System (CNS). There, they differentiate into bradyzoites, which persist in tissue cysts. Here, we investigate changes in host gene expression in the mouse brain by RNA sequencing at different time points during chronic toxoplasmosis. We show a conserved gene expression pattern caused by the infection, primarily associated with cytotoxic immune responses against the parasite and neuronal degeneration, regardless of the time point. Surprisingly, we observed that genes associated with B cell function continuously increased over time, whilst cytotoxic responses decreased. Immunoglobulin gene expression and IgA staining showed that B cells were absent from healthy brains. Following infection, they accumulated near penetrating vessels and infiltrated the brain parenchyma. Additionally, these plasma cells produced T. gondii-specific IgA. Our results show a previously unrecognized expansion of brain B cells in late chronic toxoplasmosis.