Prophylactic Administration of Gypsophila oldhamiana Extract Restricts Acute Toxoplasma gondii Infection via the DC-IL-12-CD8⁺ T Cell Axis in a Murine Model

Abstract

INTRODUCTION: Toxoplasma gondii (T. gondii) is a globally prevalent parasite that poses significant medical and veterinary challenges. Although current therapies such as pyrimethamine and sulfadiazine are effective, they often cause severe adverse effects, including myelosuppression, highlighting the need for safer and more effective alternatives. In this study, we evaluated the immunostimulatory and antiparasitic activities of three traditional herbal extracts, Stellaria dichotoma L. var. lanceolata Bge. (LDS), Stellaria aquaatic (SA) and Gypsophila oldhamiana (GO), in a murine model of T. gondii infection. METHODS: To investigate mechanisms, bone marrow-derived dendritic cells (BMDCs) were treated in vitro. For the in vivo model, C57BL/6 mice received oral extracts (100 mg/kg/day) for 13 days, starting six days prior to intraperitoneal challenge with T. gondii (ME49). Parasite burden and splenic immune profiles were analyzed at 7 days post-infection to assess acute-phase containment. RESULTS: mature dendritic cell subset and the expression of costimulatory molecules (CD40/CD80). Notably, GO simultaneously upregulated PD-L1 and PD-L2 on DCs, indicating a balanced Th1 response that prevents excessive immunopathology through checkpoint regulation while preserving strong effector functions. In vivo, GO-treated mice exhibited significantly lower splenic parasite loads than those in the control, LDS, or SA groups. GO significantly increased the frequency of IL-12-producing MHC II⁺ DCs and conventional DC type 1 (cDC1). This activation expanded IFN-γ -producing CD8⁺ and double-negative T cells, while NK cell responses were lower. CONCLUSION: Therefore, our findings show that GO extract limits acute T. gondii infection by modulating the DC-IL-12-CD8⁺ T cell axis. This study provides a modern immunological basis for the traditional use of Yinchaihu and highlights GO as a promising plant-based candidate for preventing and maintaining immunological balance during intracellular parasitic challenges.