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

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

Author information

1
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States of America.
2
Center for Inflammation, Immunity and Infection, Georgia State University, Atlanta, GA 30303, United States of America.
3
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States of America. Electronic address: dpjones@emory.edu.
4
Division of Pulmonary, Allergy and Critical Care Medicine, Emory University School of Medicine, Atlanta, GA 30322, United States of America. Electronic address: ygo@emory.edu.

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

PMID:
30999129
DOI:
10.1016/j.envint.2019.03.054
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