PM2.5 induces lung injury via mtDNA-cGAS-STING-mediated macrophage M1 polarization

作者：Bingbing Yan, Bomiao Qing, Manling Jiang, Qin Ran, Anying Xiong, Xiang He, Junyi Wang, Lei Zhang, Keyue Wang, Xiaolan Li, Guoping Li · 发表于：Frontiers in Pharmacology · 年份：2026 · DOI：10.3389/fphar.2026.1902928 · 研究领域：interferon and immune responses、Immune cells in cancer、IL-33, ST2, and ILC Pathways

Background Exposure to fine particulate matter (PM2.5) is a well-established risk factor for lung inflammation and injury. Macrophages are key innate immune cells in the lung and play critical roles in maintaining pulmonary immune homeostasis and orchestrating inflammatory responses following environmental insults. However, the precise mechanisms by which PM2.5 modulates macrophage function and contributes to lung injury remain incompletely understood. This study aimed to investigate the role of macrophage phenotypic polarization in PM2.5-induced lung injury and the underlying molecular mechanisms. Methods A subacute exposure (21-day) PM2.5 mouse model and bone marrow-derived macrophages (BMDMs) were used in vivo and in vitro to evaluate the effects of PM2.5 on pulmonary inflammation, macrophage polarization, mitochondrial injury, and cGAS-STING signaling activation. Pharmacological inhibition of cGAS was performed using RU.521 to assess the functional role of the cGAS-STING pathway in PM2.5-induced macrophage activation and lung injury. Statistical analyses were conducted to compare differences between experimental groups. Results PM2.5 exposure triggered pulmonary inflammation and tissue injury, accompanied by increased pulmonary macrophage accumulation and polarization toward the pro-inflammatory M1 phenotype. Mechanistically, PM2.5 induced mitochondrial damage in macrophages, leading to mtDNA release and subsequent activation of cGAS-STING signaling. Pharmacological inhib...