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

Environ Int. 2019 Jun;127:720-729. doi: 10.1016/j.envint.2019.03.054. Epub 2019 Apr 15.

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.

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

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cadmium / toxicity*
  • Humans
  • Inflammation / genetics
  • Influenza A Virus, H1N1 Subtype / drug effects*
  • Influenza, Human
  • Lung / drug effects
  • Lung / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Tumor Necrosis Factor-alpha
  • Cadmium