Topical Application of the Antimicrobial Agent Triclosan Induces NLRP3 Inflammasome Activation and Mitochondrial...

5-Chloro-2-(2,4-dichlorophenoxy)phenol (triclosan) is an antimicrobial chemical widely used in consumer household and clinical healthcare products. Human and animal studies have associated triclosan exposure with allergic disease. Mechanistic studies have identified triclosan as a mitochondrial uncoupler; recent studies suggest that mitochondria play an important role in immune cell function and are involved in activation of the NLRP3 inflammasome. In this study, early immunological effects were evaluated via NLRP3 activation following dermal triclosan application in a BALB/c murine model. These investigations revealed rapid caspase-1 activation and mature IL-1β secretion in the skin and draining lymph nodes (dLNs) after 1.5% and 3% triclosan exposure. Correspondingly, pro-Il-1b and S100a8 gene expression increased along with extracellular ATP in the skin. Peak gene expression of chemokines associated with caspase-1 activation occurred after 2 days of exposure in both skin tissue and dLNs. Phenotypic analysis showed an increase in neutrophils and macrophages in the dLN and myeloid and inflammatory monocytes in the skin tissue. Triclosan also caused mitochondrial dysfunction shown through effects on mitochondrial reactive oxygen species, mass, mitochondrial membrane potential, and mitochondrial morphology. These results indicate that following triclosan exposure, activation of the NLRP3 inflammasome occurs in both the skin tissue and dLNs, providing a possible mechanism for triclosan's effects on allergic disease and further support a connection between mitochondrial involvements in immunological responses.