Unraveling the role of host kinase PIM1 in Toxoplasma gondii infection: Implications for therapies.

Abstract

Toxoplasma gondii, a widespread intracellular protozoan parasite, infects a significant portion of the global human population. Restricted to an acute-infection model, this study elucidates the role of the host protein PIM1, a serine/threonine protein kinase, in facilitating T. gondii proliferation and its potential as a therapeutic target. Employing both in vitro and in vivo models, we establish that PIM1 enhances the intracellular proliferation of T. gondii by suppressing host cell apoptosis. Our findings underscore the necessity of PIM1's kinase activity in this process, as evidenced by the significant reduction in T. gondii proliferation upon treatment with either a kinase-dead PIM1 mutant or the PIM1 inhibitor AZD1208. In murine models, AZD1208 treatment resulted in decreased T. gondii load and elevated pro-apoptotic markers in tissues, indicating that PIM1 inhibition bolsters the host's immune response against the parasite. Since the role of PIM1 in chronic infection remains unexplored, follow-up studies using chronic models are essential. Collectively, our findings illuminate host-parasite interplay during acute toxoplasmosis and position PIM1 as a promising target for anti-T. gondii therapeutics.