Immunometabolic signatures induced by silver sulfide nanoparticles in freshwater clams.

Aquatic ecosystems are increasingly at risk of exposure to silver sulfide nanoparticles (Ag2S NPs) through anthropogenic waste streams, with these particles traditionally considered less toxic due to their low solubility. However, emerging evidence suggests that the oxidative dissolution of Ag2S NPs can lead to the release of silver ions (Ag+), raising questions about whether Ag2S NP-induced toxicity can be explained by Ag+ release in aquatic environments. Herein, we assess the immunotoxicity of Ag2S NPs and Ag+ in freshwater clams (Corbicula fluminea) through an immunometabolic framework. Environmental concentrations of Ag2S NPs caused substantial inflammation, broad activation of the innate immune system, and a pronounced oxidative burst, while Ag+ at equivalent silver mass mainly caused cytotoxic and did not induce immune activation. Metabolomic and transcriptomic profiling revealed distinct features of Ag2S NPs compared with Ag⁺, characterized by tissue-level glucose metabolic responses involving PPP-related features and upregulated proinflammatory signaling genes. These findings provide an immunometabolic perspective for understanding the Ag2S NP-induced toxicity, suggesting that the observed toxicity cannot be fully explained by Ag+ release during aqueous exposure and highlighting the potential ecological risk of metal sulfide nanoparticles to benthic communities. Our results suggest that Ag2S NPs pose a greater environmental hazard than previously thought, warranting further consideration in nanoparticle risk assessments.