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Environ Int. 2019 Apr 15;127:720-729. doi: 10.1016/j.envint.2019.03.054. [Epub ahead of print]
Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice.
Chandler JD1, Hu X1, Ko EJ2, Park S2, Fernandes J1, Lee YT2, Orr ML1, Hao L1, Smith MR1, Neujahr DC1, Uppal K1, Kang SM2, Jones DP3, Go YM4.
Author information
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.
Copyright ? 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
KEYWORDS:
Environmental safety; Exposome; Heavy metals; Influenza A virus; Public health
PMID: 30999129 DOI: 10.1016/j.envint.2019.03.054
Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice.
Chandler JD1, Hu X1, Ko EJ2, Park S2, Fernandes J1, Lee YT2, Orr ML1, Hao L1, Smith MR1, Neujahr DC1, Uppal K1, Kang SM2, Jones DP3, Go YM4.
Author information
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.
Copyright ? 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
KEYWORDS:
Environmental safety; Exposome; Heavy metals; Influenza A virus; Public health
PMID: 30999129 DOI: 10.1016/j.envint.2019.03.054