Phytochemicals Prime RIG-I Signaling and Th1-Leaning Responses in Human Monocyte-Derived Dendritic Cells

Background/Objective: Dendritic cells (DCs) act as sentinels bridging innate and adaptive immunity, and their functions are strongly influenced by dietary and environmental factors. Phytochemicals such as α-Mangostin (A phytochemical, a xanthone derivative from Garcinia mangostina, known for its anti-inflammatory and antioxidant properties) are widely recognized for their antioxidant and anti-inflammatory effects, but their potential to modulate antiviral pattern recognition pathways remains unclear. This study investigated whether phytochemicals activate retinoic acid–inducible gene I (RIG-I: DDX58, a cytosolic receptor recognizing viral RNA and inducing antiviral responses)–dependent signaling in human monocyte-derived dendritic cells (MoDCs) and affect downstream T cell responses. Methods: MoDCs were generated from peripheral blood and stimulated with selected phytochemicals. RIG-I pathway–related transcripts were quantified by qPCR, and protein expression was assessed by Western blotting, intracellular flow cytometry, and immunofluorescence staining. Functional outcomes were evaluated by co-culturing MoDCs with T cells, followed by phenotypic analysis via flow cytometry and measurement of IFN-γ production by ELISA. Results: α-Mangostin stimulation increased RIG-I (DDX58) mRNA levels in MoDCs and induced time-dependent changes in intracellular protein expression. In co-culture, α-Mangostin–treated MoDCs tended to increase the proportion of OX40⁺ 4-1BB⁺ CD4⁺ T cells, accompanied by a significant elevation of IFN-γ levels in supernatants. Experiments with CpG-ODN (synthetic oligodeoxynucleotides mimicking bacterial DNA that activate TLR9) suggested context-dependent crosstalk between the TLR9 and RIG-I signaling axes. Conclusions: Phytochemicals, exemplified by α-Mangostin, prime antiviral responses in human DCs through upregulation of RIG-I and promote Th1-dependent immune responses. These findings suggest that phytochemicals may represent promising nutritional strategies to enhance antiviral immunity while mitigating excessive inflammation under infectious conditions.