Lung Toxicity Induced by Co-Exposure to Particulate Matter and Indoor Microorganisms in Mice

Indoor air pollutants that significantly affect human health are often present simultaneously, leading to combined exposure. However, the toxicological effects of combined exposure on the lungs remain unclear. This study aimed to evaluate pulmonary toxicity resulting from combined exposure to dominant airborne microorganisms and particulate matter (PM). C57BL/6 mice were exposed to a combination of microorganisms and PM via intratracheal instillation for two weeks. Certain combinations of PM and microorganisms produced a marked increase in toxicity. The group co-exposed to PM and Bjerkandera adusta(fungi) showed a notable increase in eosinophil infiltration in the lungs compared to the groups treated with each agent alone. Lung histopathological changes suggestive of fibrogenesis was observed in the group co-exposed to PM and Bifidobacterium infantis(bacteria), which was not evident in the single-agent exposure groups. Transcriptomic analysis of lung tissues showed that genes strongly associated with eosinophil recruitment, such as C3 and IL-3, were synergistically upregulated in the PM and Bjerkandera adusta co-exposure groups compared to the single-agent exposure groups. Additionally, extracellular matrix-related genes, including collagen superfamily implicated in fibrosis, also exhibited positive synergistic increases in expression in the PM and Bifidobacterium infantis co-exposure groups. Overall, this study provides critical toxicological evidence that combined exposure to indoor air pollutants, such as PM and microorganisms, can induce some critical positive synergy toxicity, suggesting that the actual health risks may be greater than those previously estimated for each hazard.