Gamma irradiated soluble extracts of Toxoplasma gondii tachyzoites induced better humoral and cellular immune response due to preferential uptake by APCs scavenger receptors

Abstract

Toxoplasmosis occurs in one-third of the adult world population, without adequate vaccines and causing disease in fetus or specific groups. Aside to sterilizing effect, gamma radiation acts on antigens inducing enhanced antisera production against snake venoms or cell and humoral response to recombinant leprosy proteins. Gamma radiation affects proteins directly or indirectly in water by action of oxidant radicals from water radiolysis. Early reports showed gamma irradiated crotoxin had enhanced uptake by macrophages, limited by scavenger receptors competitors, as probucol. Irradiated tachyzoites induced adequate immune response with protection, attributed to mitotic death and DNA damage. Irradiated proteins could take a part in this process and we study the immune response induced by gamma irradiated soluble extracts of Toxoplasma gondii tachyzoites, using mice immunized with native proteins as controls. Mice immunized with irradiated extracts without adjuvants showed significant protection after challenge with ME-49 (p<0.05) and RH (p<0.0001) strains compared to controls. There are increased specific and high avidity IgG production (p<0.05) when compare d to controls group. By flow cytometry and in vitro culture, spleens of mice immunized irradiated extract presented increased proliferation of CD4+, CD8+ and B cells and IFN-γ production as compared to controls. J774 cells had increased uptake of biotinylated irradiated extracts as compared to the uptake of native extract (p<0.05), due to longer and continuous uptake. All these data points to an alternative and effective uptake and immune processing of irradiated T. gondii extracts, probably due to specific receptor of oxidized proteins as scavenger receptors, resulting in enhanced immunity. This data also implies that irradiated proteins could be involved in the protection induced by irradiated parasites. Use of antigen gamma radiation can be a simple process to enhance vaccine efficiency, avoiding the use of adjuvants.