Applied Immunology and Parasitology
01/03/2013 – 27/03/2015
Institute for Biomedical Sciences
Federal University of Uberlandia, Uberlandia, Brazil
Title: “Protection mechanisms induced by TgHSP70 immunization and inflammation control with STAg treatment in Toxoplasma gondii infection”
My PhD work focused on Toxoplasma gondii infection-associated systemic immune responses and vaccine development. I lead two main projects about distinct therapeutic approaches aiming to create potential vaccine candidates for acute and chronic toxoplasmosis. In the first, I characterized the effects of the immunization with soluble T. gondii antigen (STAg), which was based on my previous publication (Benevides et al 2013). I showed that immunized mice had less inflammation and a regulatory cytokine profile and we saw that Paneth cells in the small intestine were abrogated under T. gondii infection and immunization with STAg was not only able to dampen inflammation, but was also able to preserve Paneth cells, which are critical producers of antimicrobial peptides. In line with these findings, immunization also regulated the microbiota from a known pathogenic profile (with less E. coli and Shigella species), by protecting Paneth cells and inducing specific IgA titers against these pathogenic bacteria. The second work was based on my previous article (Czarnewski et al 2014), and I developed a recombinant vaccine using the TgHSP70 protein. We showed that mice receiving the vaccine had significantly lower parasitism and lower degree of chronic inflammation. The immunization boosted strong antibody production against natural TgHSP70. Lastly, we observed in microglial cells in the brain that stimulation/immunization with TgHSP70 significantly enhanced nitric oxide (NOS) expression and production, which was coupled with drastic reduction in parasite numbers (Czarnewski et al 2017).