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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\u2009days 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 [RSVinf]+Cd) for 16\u2009weeks. The results of inflammatory marker analysis showed that the levels of cytokines and chemokines were substantially higher in RSVinf+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 RSVinf+Cd. The metabolomics data revealed that RSVinf+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.<\/jats:p>","DOI":"10.1093\/toxsci\/kfac049","type":"journal-article","created":{"date-parts":[[2022,4,30]],"date-time":"2022-04-30T11:11:26Z","timestamp":1651317086000},"page":"62-74","source":"Crossref","is-referenced-by-count":17,"title":["Low-Dose Cadmium Potentiates Metabolic Reprogramming Following Early-Life Respiratory Syncytial Virus Infection"],"prefix":"10.1093","volume":"188","author":[{"given":"Zachery R","family":"Jarrell","sequence":"first","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University , Atlanta, Georgia 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew Ryan","family":"Smith","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University , Atlanta, Georgia 30322, USA"},{"name":"Atlanta Veterans Affairs Medical Center , Decatur, Georgia 30033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki-Hye","family":"Kim","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youri","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Hu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University , Atlanta, Georgia 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojia","family":"He","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University , Atlanta, Georgia 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Orr","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University , Atlanta, Georgia 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Opthalmology, Dean McGee Eye Institute, University of Oklahoma Health Sciences Center , Oklahoma City, Oklahoma 73104, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang-Moo","family":"Kang","sequence":"additional","affiliation":[{"name":"Center for Inflammation, Immunity & Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia 30303, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean P","family":"Jones","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University , Atlanta, Georgia 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3353-0844","authenticated-orcid":false,"given":"Young-Mi","family":"Go","sequence":"additional","affiliation":[{"name":"Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Emory University , Atlanta, Georgia 30322, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,5,5]]},"reference":[{"key":"2022062811301817500_kfac049-B1","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.metabol.2017.02.006","article-title":"Plasma metabolomics in adults with cystic fibrosis during a pulmonary exacerbation: A pilot randomized study of high-dose vitamin D3 administration","volume":"70","author":"Alvarez","year":"2017","journal-title":"Metabolism"},{"key":"2022062811301817500_kfac049-B2","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.rvsc.2020.04.018","article-title":"Effects of 1, 25-dihydroxy vitamin D3 on clinical symptoms, pro-inflammatory and inflammatory cytokines in calves with experimental pneumonia","volume":"132","author":"Asgharpour","year":"2020","journal-title":"Res. 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