Pulmonary flora-modified diesel particulate matter induced lung injury via cGAS signaling pathway

Diesel particulate matter (DPM) is a major component of Fine Particulate Matter (PM2.5), which has been recognized by the World Health Organization under the name “Class I Carcinogen”. Lung microbial communities are present widely in the lung tissue of a variety of organisms and play a significant role in the development and progression of lung disease, while cGAS is a DNA receptor that senses the invasion of microbial pathogens and activates the innate immune response. However, the role of cGAS in pulmonary flora-mediated PM2.5-induced lung injury is still largely unknown. With constructed cGAS−/− C57BL/6J mice, we found that lung damage, inflammation, and genetic damage induced by DPM were significantly blocked. With antibiotic-treated C57BL/6J mice, we found that healthy lung microbes were able to attenuate DPM-induced lung damage, inflammation, and genetic damage. DPM modified the expression of the cGAS/STING signaling pathway through the lung flora. This study revealed that cGAS signaling pathway played an essential role in lung flora-mediated adverse effects of DPM, which provided new therapeutic targets for lung diseases.