Low-Dose Cadmium Potentiates Metabolic Reprogramming Following Early-Life Respiratory Syncytial Virus Infection. (5th May 2022)

• Record Type: Journal Article
• Authors: Jarrell, Zachery R; Smith, Matthew Ryan; Kim, Ki-Hye; Lee, Youri; Hu, Xin; He, Xiaojia; Orr, Michael; Chen, Yan; Kang, Sang-Moo; Jones, Dean P; Go, Young-Mi
• Is Part Of: Toxicological sciences. Volume 188:Number 1(2022)
• Page Start: 62
• Page End: 74
• Publication Date: 2022-05-05
• Subjects: early life exposure -- dietary metal -- environmental stressor -- lung pathology -- metabolic disruption -- pulmonary fibrosis; Toxicology -- Periodicals; Toxicology -- Periodicals; Toxicology; Periodicals; 615.9
• DOI: 10.1093/toxsci/kfac049
• Languages: English
• ISSNs: 1096-6080

Abstract

Abstract: Respiratory syncytial virus (RSV) infection causes serious pulmonary disease and death in high-risk infants and elderly. Cadmium (Cd) is a toxic environmental metal contaminant and constantly exposed to humans. Limited information is available on Cd toxicity after early-life respiratory virus infection. In this study, we examined the effects of low-dose Cd exposure following early-life RSV infection on lung metabolism and inflammation using mouse and fibroblast culture models. C57BL/6J mice at 8 days old were exposed to RSV 2 times with a 4-week interval. A subset of RSV-infected mice was subsequently treated with Cd at a low dose in drinking water (RSV infection at infant age [RSV inf ]+Cd) for 16 weeks. The results of inflammatory marker analysis showed that the levels of cytokines and chemokines were substantially higher in RSV inf +Cd group than other groups, implying that low-dose Cd following early-life RSV infection enhanced lung inflammation. Moreover, histopathology data showed that inflammatory cells and thickening of the alveolar walls as a profibrotic signature were evident in RSV inf +Cd. The metabolomics data revealed that RSV inf +Cd-caused metabolic disruption in histamine and histidine, vitamin D and urea cycle, and pyrimidine pathway accompanying with mechanistic target of rapamycin complex-1 activation. Taken together, our study demonstrates for the first time that cumulative Cd exposure following early-life RSV infection has a significant impact on subsequent inflammation and lung metabolism. Thus, early-life respiratory infection may reprogram metabolism and potentiate Cd toxicity, enhance inflammation, and cause fibrosis later in life.