RT Journal Article
SR Electronic
T1 Low-dose cadmium potentiates lung inflammatory response to 2009 pandemic H1N1 influenza virus in mice
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 346866
DO 10.1101/346866
A1 Joshua D. Chandler
A1 Xin Hu
A1 Eunju Ko
A1 Soojin Park
A1 Jolyn Fernandes
A1 Young-Tae Lee
A1 Michael L. Orr
A1 Li Hao
A1 M. Ryan Smith
A1 David C. Neujahr
A1 Karan Uppal
A1 Sang-Moo Kang
A1 Dean P. Jones
A1 Young-Mi Go
YR 2018
UL http://biorxiv.org/content/early/2018/06/14/346866.abstract
AB 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. Using histopathology and flow cytometry, we observed increased lung inflammation in Cd-treated mice given H1N1 compared to H1N1 alone, including neutrophils, monocytes, T lymphocytes and dendritic cells. 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.AbbreviationsCdCadmiumCtlcontrolCyscysteineCySScystineFACSfluorescence-activated cell sortingFDRFalse discovery rateGSEAGene set enrichment analysisH1N1pandemic 2009 influenza A (H1N1) virusHRMHigh resolution metabolomicsICP-MSInductively coupled plasma mass spectrometerinterferon gammaIFN-γinterleukin-1betaIL-1βLCliquid chromatographMSmass spectrometerm/zmass to chargeRTretention timesPLSsparse partial least squaresTrxthioredoxin