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

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, naive 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.

Automated summary

Experimental toxoplasmosis serves as a valuable model to study adaptive immune responses. Gamma-irradiated tachyzoites and soluble tachyzoite antigen extracts (STags) can protect mice against experimental toxoplasmosis. Scavenger receptors, particularly CD36, play a role in recognizing irradiated proteins and promoting antigen presentation. CD36 deficiency results in an altered immune response, with CD36(-/-) mice showing immune defects when infected with cyst-forming Toxoplasma gondii. In this study, CD36(-/-) mice, whether naive or immunized with gamma-irradiated STags, were unable to resist viable RH tachyzoites. They exhibited poor humoral responses despite normal levels of serum immunoglobulins. Irradiated antigens failed to induce antibody production in CD36(-/-) mice, but when transplanted with irradiated STag-primed wild-type macrophages, adequate levels of immunoglobulin G were produced. CD36 is crucial for the humoral response against the irradiated antigen, although other pathways are also involved in mounting a humoral response against any antigen. CD36 plays a role in lipid and free fatty acid transport as well as in the immune response, and gamma radiation mimics the innate response by targeting irradiated antigens of this pathway.