Dietary Aflatoxin G1 exposure causes an imbalance between pulmonary tissue-resident alveolar macrophages and monocyte-derived macrophages in both mother and offspring mice

Aflatoxin G 1 (AFG 1 ) is a mycotoxin commonly found in agricultural products, including dried fruits, meat, and milk products. Oral AFG 1 administration induced tumor necrosis factor (TNF)-α-dependent chronic pulmonary inflammation, promoting AFG 1 -induced damage in alveolar epithelial cell, which is associated with lung adenocarcinoma. Pulmonary macrophages may be divided into tissue-resident alveolar macrophages (TRAMs) and monocyte-derived macrophages (MoMs), which involve in chronic lung inflammation. However, whether these macrophages contribute to AFG 1 -induced chronic pulmonary inflammation remains unknown. In this study, we found oral AFG 1 administration disrupted the balance between TRAMs and MoMs, increasing MoMs infiltration and decreasing the number of TRAMs. AFG 1 upregulated TNF-α expression in MoMs, but downregulated sialic acid binding Ig-like lectin F (Siglec-F) expression in TRAMs. Inhibition of TNF-α-dependent inflammation rescued the imbalance between TRAMs and MoMs in AFG 1 -treated lung tissues. Additionally, AFG 1 stimulated MoMs differentiation to the proinflammatory M1 phenotype in vitro. Using a specific in vitro TRAM model, AFG 1 downregulated Siglec-F and the M2 phenotypic markers arginase 1 and YM1, and upregulated the M1 phenotypic markers IL-6, iNOS and TNF-α, altering the TRAMs phenotype to the pro-inflammatory M1 phenotype in vitro . Additionally, mouse maternal dietary exposure to AFG 1 caused an imbalance in pulmonary macrophages, decreasing TRAMs and increasing MoMs population in offspring, which was associated with proliferative lesions in the alveolar septa. Thus, dietary AFG 1 exposure triggered an imbalance in pulmonary macrophages in both mother and offspring mice, and induced pro-inflammatory phenotypic alterations, which contributed to AFG 1 -induced chronic lung inflammation. These results provide clues to how AFG 1 -induced immunotoxicity and genotoxicity in humans might be prevented. • AFG 1 disrupted the balance between TRAMs and MoMs in mother and offspring mice. • TNF-α-dependent lung inflammation regulated the imbalance between TRAMs and MoMs. • AFG 1 increased MoMs number and stimulated it differentiation to pro-inflammatory M1. • AFG 1 decreased TRAMs number and altered TRAMs phenotype to pro-inflammatory M1. • Maternal dietary exposure to AFG 1 increased MoMs number and decreased TRAMs number.