Beyond Rejection: Exploring Tacrolimus's Hidden Potential in Toxoplasmosis

Human infection and treatment of Toxoplasma gondii, known as toxoplasmosis, pose unique challenges and risks, particularly in transplant recipients and immunocompromised individuals. Toxoplasma gondii is an apicomplexan protozoan parasite that has been defined as the most successful parasite, with infections ranging from asymptomatic to fatal. It is prevalent throughout the world, presenting higher morbidity and mortality in immunocompromised and immunosuppressed individuals. Tacrolimus is a calcineurin inhibitor, often serving a role in transplant medicine as an immunosuppressant. Cyclosporine is the other commonly used calcineurin inhibitor, with similarity to tacrolimus in its mechanism of action, and has shown to be effective in the treatment of several parasitic infections. Both of these drugs block the intracellular calcium signaling cascade mediated by calcineurin, through binding to their respective immunophilin proteins. Toxoplasma gondii is dependent on this pathway for cell lysis and its egress from the vacuole. Cyclosporine has presented antiparasitic activity both in vitro and in vivo against another protozoan parasite with similarities to T. gondii, Plasmodium falciparum, through its inhibition of this pathway. Given the functional similarities between cyclosporine and tacrolimus, this narrative review aims to assess the antiparasitic potential of tacrolimus, particularly considering the promising antiparasitic activity observed with cyclosporine and other calcineurin inhibitors. Further research is needed on this role in tacrolimus to evaluate its efficacy, safety, and other potentials in the management of toxoplasmosis, independently and in combination therapies.