Work

Trem2 prevents adverse pregnancy outcomes induced by Toxoplasma gondii by promoting PPARγ-mediated P-STAT6 signaling

Year: 2025

Type: article

Abstract: Decidual macrophages (DMs), required for the maintenance of a successful pregnancy, are vital target cells for Toxoplasma gondii (T. gondii) during adverse pregnancy induced by T. gondii. Triggering receptor expressed on myeloid cells 2 (Trem2) is a functional immune receptor on the surface of DMs, governing cell survival and phagocytosis. Our previous study demonstrated that Trem2 deficiency aggravates T. gondii-induced APOs. However, Trem2-related downstream signaling pathways in T. gondii-induced APOs remain unclear. Here, we demonstrated a significant decrease in PPARγ and phosphorylated-STAT6 (P-STAT6) in mouse placentas following T. gondii infection. Following knockout of the Trem2 gene, we found that T. gondii infection cannot regulate the expression of downstream signaling pathways on macrophages. Hence, Trem2 deficiency did not alter the expressions of P-STAT6 and PPARγ in infected mouse placentas, peritoneal macrophages, and bone marrow-derived macrophages (BMDMs). Consistently, overexpression of Trem2 in macrophages significantly activated the downstream signaling pathway and partially reversed the inhibitory effects of T. gondii antigens on P-STAT6 and PPARγ, similar to the effect of PPARγ agonists. Altogether, Trem2 is required for T. gondii to exert effects on P-STAT6/PPARγ in APOs. Our novel findings concerning Trem2 and its downstream PPARγ-mediated P-STAT6 signaling pathways might provide new preventive and therapeutic targets for toxoplasmosis.

Source: International Immunopharmacology

DOI: 10.1016/j.intimp.2025.115739