Contrasting outcomes and mechanisms of immunotoxicity of different water-soluble tungsten species in zebrafish (Danio rerio).

Exposure to tungsten, an emerging pollutant, is linked to cancer incidence and causes immune dysfunction. Till date the impact of tungsten speciation on immunotoxicity remains unclear. Here, we contrasted the immunotoxic effects of monomeric tungstate (W1) and polytungstate, the main forms of tungsten in environmental waters, on adult zebrafish, following static short-term (14 days) exposure to 0-215 mg L-1 tungsten. In the W1- and phosphotungstate (PW12)-treated systems, W1 was the dominant species that accounted for > 92 % tungsten, whereas metatungstate (W12) mainly (>59 %) existed as polytungstates with 2, 4, and 6 tungsten atoms. W1 exposure caused 1 % mortality, with tungsten primarily accumulating in metabolically active organs, brain, and gill. Contrastingly, polytungstate exposure caused up to 75 % mortality and 16 times higher tungsten bioaccumulation. Furthermore, polytungstate predominantly accumulated in the immune organs, intestine, and spleen, leading to intestinal villi necrosis and splenic melano-macrophage accumulation. Based on intestinal and splenic transcriptome analysis, W1 exposure upregulated the cytosolic DNA-sensing pathway, whereas polytungstate exposure downregulated the nucleotide-binding oligomerization domain-like and C-type lectin receptor signaling pathways. Polytungstate exposure also disturbed inflammatory factor expression, consistent with severe immunosuppression and inflammatory damage. These findings demonstrate that tungsten speciation regulates its uptake and accumulation, as well as the immunosuppression and inflammatory responses. Future tungsten toxicity assessment should rigorously account for its speciation. ENVIRONMENTAL IMPLICATION: Tungsten forms tungstate and many polytungstate complexes in environmental waters. Here, we systematically evaluated how this diverse speciation would impact the immunotoxicity of tungsten to aquatic organisms and potentially humans, using the zebrafish model. Short-term polytungstate exposure caused markedly higher mortality, greater bioaccumulation particularly in the immune organs, more striking histopathological abnormalities, and more severe immunosuppression and inflammatory damage than tungstate exposure. These results highlight the need to quantitatively assess tungsten speciation for a holistic understanding of the health impacts of tungsten exposure and will support the management and risk assessment of tungsten contamination in aquatic environments.