Immunomodulation by extracellular vesicle-like nanoparticles from marine macroalgae Sargassum fusiforme: Enhancing Type 1 T helper and cytotoxic T lymphocyte-mediated immune responses

Abstract

This study investigated the immunological features and therapeutic potential of extracellular vesicle-like nanoparticles isolated from the marine macroalgae Sargassum fusiforme (SF-NPs). SF-NPs were approximately 266.4 nm in size, and comprehensive metabolomic analysis revealed 38 metabolites. SF-NPs can upregulate dendritic cell (DC) maturation markers, increase pro-inflammatory cytokine production, and enhance antigen presentation capacity. DC maturation is regulated by the mitogen-activated protein kinase and nuclear factor-kappa B pathways. Notably, SF-NPs-primed DCs orchestrated robust CD4+ and CD8+ T-cell proliferation, fostering potent Type 1 T-helper(Th1) responses and cytotoxic T lymphocyte (CTL) activity. In a cyclophosphamide-induced immunosuppression mouse model, SF-NPs restored and activated immune cell populations, including DCs, natural killer, CD4+ T, and CD8+ T cells. SF-NPs reversed cyclophosphamide-induced Type 2 T-helperand regulatory T cell-biased responses, favoring Th1 and CTL responses, including multifunctional T cell responses. This study highlighted the potential of SF-NPs as therapeutic candidates for diseases requiring Th1 and CTL responses.