Dopamine-induced mitochondrial dysfunction activates cGAS-sTING to drive IL-6 secretion in macrophages.

Dopamine induces mitochondrial stress that activates the cGAS-STING pathway, leading to IL-6 secretion in primary human macrophages.

• Why it matters: Understanding how dopamine influences innate immune responses is crucial, as it may explain variability in systemic inflammation and immune regulation among individuals.
• What they did: The study examined primary human monocyte-derived macrophages and found that dopamine causes mitochondrial depolarization, alters mitochondrial dynamics, and promotes mtDNA release, which activates cGAS-STING and NF-κB signaling; variability in dopamine receptor expression correlates with IL-6 responses.
• The result: Blocking mitochondrial dysfunction or cGAS-STING signaling reduces IL-6 secretion, suggesting these pathways are key mediators of dopamine-driven inflammation and may underlie individual differences in immune responses.