Toxoplasma gondii in CD36 -/- mice shows lethal infection and poor immunization with probable macrophage immune...

Experimental toxoplasmosis is an excellent model for adaptive immune response. Gamma-irradiated tachyzoites or soluble tachyzoite antigen extracts (STag) induce protection against experimental toxoplasmosis in mice. Scavenger receptors recognize irradiated proteins, promote their entry into cells, and lead to antigen presentation. CD36 is a specific scavenger receptor involved in intracellular transport of free fatty acid (FFA), cellular recycling, and intracellular trafficking in lipid rafts outside the lysosomal pathways. CD36 is also associated with an altered immune response, as CD36^-/- mice presented some immune defects in the cyst-forming Toxoplasma gondii. We studied T. gondii infection in CD36^-/- mice, naïve or immunized, with irradiated T. gondii STags by investigating protection, antibody production, and primed macrophage transplantation. CD36^-/- mice presented no resistance against the viable RH tachyzoites, even after immunization with gamma-irradiated STags that protected wild-type mice. The animals presented poor humoral responses to both immunogens despite adequate levels of serum immunoglobulins. CD36^-/- mice failed to induce protection against virulent T. gondii infection with inadequate antibody production or an innate response. Irradiated antigens failed to induce antibodies in CD36^-/- mice and only produced adequate levels of immunoglobulin G when transplanted with irradiated STag-primed wild-type macrophages. The CD36 pathway is necessary for humoral response against the irradiated antigen; however, several other pathways are also involved in mounting a humoral response against any antigen. CD36 is a multipurpose molecule for FFA and lipid transport, as well as for the immune response, and gamma radiation mimics the innate response by targeting irradiated antigens of this pathway.