Differential Regulation of Hepatic Akt/mTOR Signaling During Acute and Chronic Toxoplasma gondii Infection in a Murine Model

Toxoplasma gondii is an obligate intracellular parasite that infects virtually all warm-blooded animals, progressing through acute and chronic stages. The Akt/mTOR signaling axis plays critical roles in cell survival, proliferation, and metabolism, making it a key target for intracellular pathogens. This study investigated how T. gondii infection modulates this pathway during both infections. Outbred CD-1 mice were infected intraperitoneally with the virulent GT1 strain of T. gondii . Mice for acute studies were sacrificed five days post-infection, while those for chronic studies were treated with sulfadiazine and sacrificed five months post-infection. Phosphoprotein expression of eight Akt/mTOR pathway components was measured in liver tissues using a multiplexed bead-based immunoassay. Acute T. gondii infection caused broad suppression of Akt/mTOR signaling, with 6 of 8 markers significantly downregulated, including pS6RP ^Ser235/236 , pAKT ^S473 , pBAD ^Ser136 , pIRS1 ^S636/639 , pPTEN ^Ser380 , and pGSK-3α/β ^Ser21/9 . In contrast, chronic infection selectively activates specific nodes of the pathway in a cyst burden-dependent manner, including pBAD ^Ser136 , pmTOR ^Ser2448 , and pGSK-3α/β ^Ser21/ 9. There are strong correlations in signaling changes between inter-components, which reflect coherent and coordinated pathway-level reprogramming rather than random perturbation. These findings show that acute and chronic T. gondii infections have opposing effects on host Akt/mTOR signaling for their own benefit, which may present new therapeutic targets.