Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice. (June 2019)

• Record Type: Journal Article
• Authors: Chandler, Joshua D.; Hu, Xin; Ko, Eun-Ju; Park, Soojin; Fernandes, Jolyn; Lee, Young-Tae; Orr, Michael L.; Hao, Li; Smith, M. Ryan; Neujahr, David C.; Uppal, Karan; Kang, Sang-Moo; Jones, Dean P.; Go, Young-Mi
• Is Part Of: Environment international. Volume 127(2019)
• Page Start: 720
• Page End: 729
• Publication Date: 2019-06
• Subjects: Cd cadmium -- Ctrl control -- Cys cysteine -- CySS cystine -- FACS fluorescence-activated cell sorting -- FDR false discovery rate -- GSEA gene set enrichment analysis -- H1N1 pandemic 2009 influenza A (H1N1) virus -- HRM high resolution metabolomics -- ICP-MS inductively coupled plasma mass spectrometer -- IFNγ interferon gamma -- IL-1β interleukin-1beta -- LC liquid chromatograph -- MS mass spectrometer -- m/z mass to charge -- RT retention time -- sPLS sparse partial least squares -- Trx thioredoxin; Environmental safety -- Exposome -- Heavy metals -- Influenza A virus -- Public health; Environmental protection -- Periodicals; Environmental health -- Periodicals; Environmental monitoring -- Periodicals; Environmental Monitoring -- Periodicals; Environnement -- Protection -- Périodiques; Hygiène du milieu -- Périodiques; Environnement -- Surveillance -- Périodiques; Environmental health; Environmental monitoring; Environmental protection; Periodicals; 333.705
• DOI: 10.1016/j.envint.2019.03.054
• Languages: English
• ISSNs: 0160-4120

Abstract

Abstract: Cadmium (Cd) is a toxic, pro-inflammatory metal ubiquitous in the diet that accumulates in body organs due to inefficient elimination. Responses to influenza virus infection are variable, particularly severity of pneumonia. We used a murine model of chronic low-dose oral exposure to Cd to test if increased lung tissue Cd worsened inflammation in response to sub-lethal H1N1 infection. The results show that Cd-treated mice had increased lung tissue inflammatory cells, including neutrophils, monocytes, T lymphocytes and dendritic cells, following H1N1 infection. Lung genetic responses to infection (increasing TNF-α, interferon and complement, and decreasing myogenesis) were also exacerbated. To reveal the organization of a network structure, pinpointing molecules critical to Cd-altered lung function, global correlations were made for immune cell counts, leading edge gene transcripts and metabolites. This revealed that Cd increased correlation of myeloid immune cells with pro-inflammatory genes, particularly interferon-γ and metabolites. Together, the results show that Cd burden in mice increased inflammation in response to sub-lethal H1N1 challenge, which was coordinated by genetic and metabolic responses, and could provide new targets for intervention against lethal inflammatory pathology of clinical H1N1 infection. Graphical abstract: Unlabelled Image Highlights: Low environmental Cd potentiated lung inflammation by influenza virus infection in mice. Cd-increased inflammation was coordinated by genetic and metabolic responses. Combination of pathology with data-driven omics supports analysis of toxicologic effects at low environmental Cd exposure.