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Eine Plattform für die Wissenschaft: Bauingenieurwesen, Architektur und Urbanistik
Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice
https://orcid.org/0000-0003-3353-0844
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 Display Omitted
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.
Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice
https://orcid.org/0000-0003-3353-0844
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 Display Omitted
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.
Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice
https://orcid.org/0000-0003-3353-0844
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 Display Omitted
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.
Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice
Chandler, Joshua D. (Autor:in) / Hu, Xin (Autor:in) / Ko, Eun-Ju (Autor:in) / Park, Soojin (Autor:in) / Fernandes, Jolyn (Autor:in) / Lee, Young-Tae (Autor:in) / Orr, Michael L. (Autor:in) / Hao, Li (Autor:in) / Smith, M. Ryan (Autor:in) / Neujahr, David C. (Autor:in)
Environmental International ; 127 ; 720-729
24.03.2019
10 pages
Aufsatz (Zeitschrift)
Elektronische Ressource
Englisch
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 , <italic>m</italic>/<italic>z</italic> , mass to charge , RT , retention time , sPLS , sparse partial least squares , Trx , thioredoxin , Environmental safety , Exposome , Heavy metals , Influenza A virus , Public health
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