Análise temporal de RNA-seq revela infiltração de células B durante a toxoplasmose cerebral crônica

Abstract

Chronic toxoplasmosis is characterized by the persistence of Toxoplasma gondii in the central nervous system, where the tachyzoites convert to bradyzoites and remain undetected. Here, we sought to identify markers that would be expressed in the brain in early (21 and 28 days), and late (3 and 6 months) chronic infection by performing High-throughput RNA sequencing analysis using a publicly available RNAseq dataset. We show a conserved gene expression pattern caused by the infection, primarily associated with pro-inflammatory immune responses against the parasite and neuronal degeneration, regardless of the time points. Surprisingly, we observed that genes associated with B cell function continuously increased over time, while those associated with cytotoxic responses decreased. Inspection of immunoglobulin related genes and immunostaining for IgA confirmed that B cells were not found in the brain of uninfected mice, but after infection, concentrated in the meninges and vicinity of vessels that penetrate the central nervous system and some of them were able to enter the brain parenchyma. Our results show a previously undescribed expansion of B cells producing IgA in the brain in chronic toxoplasmosis.