Respiratory toxicity of perfluorooctanesulfonic acid (PFOS) via Inflammasome involvement

Per- and polyfluoroalkyl substances (PFAS), widely used as durable additives in various consumer products for their water- and oil-repellent properties, persist environmentally and bioaccumulate, raising substantial health concerns. The primary route of human exposure towards PFAS is via contaminated food and drinking water, however, mounting evidence highlights inhalation as additional, critical route of exposure. In particular, inhalation of perfluorooctane sulfonate (PFOS) adversely affects respiratory health through immune disruption, oxidative stress, and impaired barrier function, particularly evident during prenatal exposure. Recent evidence reveals that emerging, anthropogenic PFOS exposure activates innate immune pathways conserved over millions of years of evolution leading to inflammation and tissue injury. PFOS has been shown to trigger the AIM2 inflammasome via mitochondrial damage and DNA release, inducing pyroptosis and IL-1β secretion leading to prolonged inflammation and tissue injury. Beyond inflammasomes, the cGAS/STING axis, which is closely co-regulated with the inflammasome, recognizes ectopic DNA and contributes to PFOS-induced inflammatory responses. Co-exposures to airborne pollutants or infections might additionally amplify these effects, as demonstrated by increased expression of AIM2, cGAS, and STING in lung cells following bacterial or particulate challenges. This commentary highlights the critical need for mechanistic research on PFOS-triggered innate immune signalling and potential harmful co-exposure interactions particularly in the lung to better assess health risks and inform regulatory policies for these persistent environmental contaminants.