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

Yangxuan Wei; Xiaoyan Liang; Yulin Wu; Jiayu Zhang; Xiaohui Cui; Yutong Wu; Delin Zhu; Ping Lv; Wei Meng; Wenbin Li; Haitao Shen

doi:10.1016/j.ecoenv.2024.117082

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

Ecotoxicol Environ Saf. 2024 Sep 23:285:117082. doi: 10.1016/j.ecoenv.2024.117082. Online ahead of print.

Authors

Yangxuan Wei¹, Xiaoyan Liang², Yulin Wu³, Jiayu Zhang⁴, Xiaohui Cui³, Yutong Wu³, Delin Zhu³, Ping Lv⁵, Wei Meng⁶, Wenbin Li⁷, Haitao Shen⁸

Affiliations

¹ Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China; Department of Pathophysiology, Neuroscience Research Center, Hebei Medical University, Shijiazhuang, China.
² Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China; Department of Pathology, Hebei Reproductive Health Hospital, Shijiazhuang, China.
³ Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China.
⁴ Center of Metabolic Diseases and Cancer Research (CMCR), Hebei Medical University, Shijiazhuang, China.
⁵ Department of Pharmacology, Hebei Medical University, Shijiazhuang, China.
⁶ Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China; Department of Pathology, The First Hospital of Handan, Handan, China. Electronic address: 15713293285@163.com.
⁷ Department of Pathophysiology, Neuroscience Research Center, Hebei Medical University, Shijiazhuang, China. Electronic address: liwbsjz@hebmu.edu.cn.
⁸ Laboratory of Pathology, Hebei Medical University, Shijiazhuang, China; Center of Metabolic Diseases and Cancer Research (CMCR), Hebei Medical University, Shijiazhuang, China; Hebei Collaborative Innovation Center of Tumor Microecological Metabolism Regulation, Affiliated Hospital of Hebei University, Baoding, Hebei, China. Electronic address: haitaoshen78@hebmu.edu.cn.

PMID: 39317075
DOI: 10.1016/j.ecoenv.2024.117082

Abstract

Aflatoxin G₁ (AFG₁) is a mycotoxin commonly found in agricultural products, including dried fruits, meat, and milk products. Oral AFG₁ administration induced tumor necrosis factor (TNF)-α-dependent chronic pulmonary inflammation, promoting AFG₁-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 AFG₁-induced chronic pulmonary inflammation remains unknown. In this study, we found oral AFG₁ administration disrupted the balance between TRAMs and MoMs, increasing MoMs infiltration and decreasing the number of TRAMs. AFG₁ 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 AFG₁-treated lung tissues. Additionally, AFG₁ stimulated MoMs differentiation to the proinflammatory M1 phenotype in vitro. Using a specific in vitro TRAM model, AFG₁ 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 AFG₁ 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 AFG₁ exposure triggered an imbalance in pulmonary macrophages in both mother and offspring mice, and induced pro-inflammatory phenotypic alterations, which contributed to AFG₁-induced chronic lung inflammation. These results provide clues to how AFG₁-induced immunotoxicity and genotoxicity in humans might be prevented.

Keywords: Aflatoxin G(1) (AFG(1)); Lung inflammation; Monocyte-derived macrophages (MoMs); Tissue-resident alveolar macrophages (TRAMs).