TREM2 plays a critical role in innate immune defense against acute Toxoplasma gondii infection by promoting macrophage antimicrobial activities

We investigated the function of TREM2 during acute Toxoplasma gondii infection by comparing TREM2-deficient and C57BL/6 wild-type (WT) mice during intraperitoneal infection with type II (Prugniaud strain) T. gondii. Infected TREM2 knockout (KO) mice had significantly increased mortality and elevated parasite burden during acute infection, as well as increased liver pathology and higher levels of inflammatory cytokines IL-1, IL-6, and IL-17A by 7 days post-infection (dpi).

Notably, we observed an early expansion and dissemination of T. gondii in infected macrophages in the omentum in TREM2 KO compared to WT mice, and this phenotype was specific to TREM2 deficiency on radiation-sensitive cells, based on bone marrow chimera experiments. In vitro, TREM2 KO macrophages were more permissive to T. gondii infection and exhibited reduced LAMP-1 upregulation and impaired phagocytotic clearance of T. gondii compared to WT macrophages.