Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice

• Main Authors: Joshua D. Chandler, Xin Hu, Eun-Ju Ko, Soojin Park, Jolyn Fernandes, Young-Tae Lee, Michael L. Orr, Li Hao, M. Ryan Smith, David C. Neujahr, Karan Uppal, Sang-Moo Kang, Dean P. Jones, Young-Mi Go
• Format: Article
• Language: English
• Published: Elsevier 2019-06-01
• Series: Environment International
• Online Access: http://www.sciencedirect.com/science/article/pii/S0160412018332045

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. Keywords: Environmental safety, Exposome, Heavy metals, Influenza A virus, Public health