Host kynurenine monooxygenase (KMO) serves as a critical immune defense factor restricting Toxoplasma gondii proliferation.

Toxoplasma gondii is an obligate intracellular protozoan parasite capable of infecting virtually all warm-blooded animals. The kynurenine pathway (KP), a key route of tryptophan catabolism, serves as a critical immunometabolic checkpoint in cancer, autoimmune disorders, and neurodegenerative diseases. Although the kynurenine monooxygenase (KMO)-derived metabolite quinolinic acid (QUIN) has well-documented antiviral effects, its role in antiparasitic immunity remains unexplored. Here, we identify KMO as a critical mediator of host defense against T. gondii. Upon infection, T. gondii significantly suppresses host KMO expression along with its downstream metabolites, including 3-hydroxykynurenine (3-HK) and QUIN. Functional studies in Vero cells demonstrate that KMO overexpression effectively restricts parasite proliferation, whereas RNA interference (RNAi)-mediated knockdown (KD) of KMO increases parasite burden. Collectively, these findings establish KMO as a non-canonical determinant of anti-T. gondii immunity and nominate KP potentiation as a therapeutic strategy for toxoplasmosis.