Immunity in the spleen and blood of mice immunized with irradiated Toxoplasma gondii tachyzoites

Abstract

Toxoplasma gondii infection induces a strong and long-lasting immune response that is able to prevent most reinfections but allows tissue cysts. Irradiated, sterilized T. gondii tachyzoites are an interesting vaccine, and they induce immunity that is similar to infection, but without cysts. In this study, we evaluated the cellular immune response in the blood and spleen of mice immunized with this preparation by mouth (v.o.) or intraperitoneally (i.p.) and analyzed the protection after challenge with viable parasites. BALB/c mice were immunized with three i.p. or v.o. doses of irradiated T. gondii tachyzoites. Oral challenge with ten cysts of the ME-49 or VEG strain at 90 days after the last dose resulted in high levels of protection with low parasite burden in the immunized animals. There were higher levels of specific IgG, IgA and IgM antibodies in the serum, and the i.p. immunized mice had higher levels of the high-affinity IgG and IgM antibodies than the orally immunized mice, which had more high-affinity IgA antibodies. B cells (CD19(+)), plasma cells (CD138(+)) and the CD4(+) and CD8(+) T cell populations were increased in both the blood and spleen. Cells from the spleen of the i.p. immunized mice also showed antigen-induced production of interleukin-10 (IL-10), interferon gamma (IFN-γ) and interleukin 4 (IL-4). The CD4(+) T cells, B cells and likely CD8(+) T cells from the spleens of the i.p. immunized mice proliferated with a specific antigen. The protection was correlated with the spleen and blood CD8(+) T cell, high-affinity IgG and IgM and antigen-induced IL-10 and IL-4 production. Immunization with irradiated T. gondii tachyzoites induces an immune response that is mediated by B cells and CD4(+) and CD8(+) T cells, with increased humoral and cellular immune responses that are necessary for host protection after infection. The vaccine is similar to natural infection, but free of tissue cysts; this immunity restrains infection at challenge and can be an attractive and efficient model for vaccine development in toxoplasmosis.

Transcriptional Responses in the Murine Spleen after Toxoplasma gondii Infection: Inflammasome and Mucus-Associated Genes

“…This is in line with previous reports describing increased splenic expression of these genes after T. gondii infection [4,14,28,29,30]. In human monocytes, particularly the secreted GRA15 protein of T. gondii is responsible for IL-1β induction and the release of IL-1β is a direct consequence of inflammasome activation after infection [31].…”

Host Cell Vimentin Restrains Toxoplasma gondii Invasion and Phosphorylation of Vimentin is Partially Regulated by Interaction with TgROP18

“…Strong and persistent cell-mediated immunity, mainly Th1 responses, is activated by T. gondii infection, and can protect the host from rapid tachyzoite proliferation and consequent pathology 48 , 49 . CD4 + and CD8 + T cell populations are increased in the spleens of mice immunized with T. gondii 50 ; therefore, although low expression levels of vimentin were also observed in this organ, it develops no more cysts than other tissues.…”

Resposta imunológica em modelos animais imunizados contra o muco nativo ou irradiado por raios gama de ⁶⁰Co da raia de água doce <i>Paratrygon aiereba</i>

“…Além disso, a radiação gama tem se demonstrado útil na atenuação ou esterilização de agentes biológicos dos mais variados tipos, por promover a perda da capacidade reprodutiva, no caso de parasitas intracelulares e outros microrganismos, (Hiramoto, 2002), mantendo o potencial imunogênico adequado (Costa, 2013;Zorgi et al, 2016).…”

“…Apesar dos níveis de anticorpos quantificados no IVIAP terem sido menores que os do ELISA, podemos destacar a capacidade dos anticorpos anti-muco irradiado de reconhecer e responder ao muco na sua forma nativa, e dos esplenócitos dos animais imunizados contra o muco irradiado serem mais responsivos do que os demais grupos (imunizados contra o muco nativo e não imunizados). Esses dados estão de acordo com trabalhos que utilizam a irradiação de toxinas ou venenos de serpentes e de parasitas, pois a radiação gama é capaz de melhorar as propriedades imunogênicas destes compostos (Camilo et al, 2005;Zorgi et al, 2016). E assim como no trabalho desenvolvido por Hiramoto (2002), investigando a produção de anticorpos anti-Toxoplasma gondii após a imunização com taquizoítos irradiados, os títulos de anticorpos resultantes do ensaio por IVIAP também foi inferior aos do ELISA, assim como neste estudo.…”