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

• Authors: Joshua Chandler, Emory University; Xin Hu, Emory University; Eunju Ko, Georgia State University; Soojin Park, Georgia State University; Jolyn Fernandes, Emory University; Young-Tae Lee, Georgia State University; Michael L. Orr, Emory University; Li Hao, Emory University; M. Ryan Smith, Emory University; David Neujahr, Emory University; Karan Uppal, Emory University; Sang-Moo Kang, Georgia State University; Dean Jones, Emory University; Young-Mi Go, Emory University
• Journal Title: Environment International
• Volume: Volume 127
• Publisher: Elsevier Science Ltd. | 2019-06-01, Pages 720-729
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1016/j.envint.2019.03.054
• Subjects: Biology, Virology; Environmental Sciences; Health Sciences, Public Health; Biology, Genetics
• Keywords: Science & Technology; Life Sciences & Biomedicine; Environmental Sciences; Environmental Sciences & Ecology; Environmental safety; Exposome; Heavy metals; Influenza A virus; Public health; NF-KAPPA-B; Respiratory syncytial virus; Regulatory factor 1; Chronic exposure; National health; Gene; Transcription; Expression; Blood; Gamma

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.