Dataset Information

Early life arsenic exposure and acute and long-term responses to influenza A infection in mice.

ABSTRACT:

Background

Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood.

Objective

We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice.

Methods

C57BL/6 mice were exposed to arsenic in utero and throughout postnatal life. At 1 week of age, a subgroup of mice were infected with influenza A. We then assessed the acute and long-term effects of arsenic exposure on viral clearance, inflammation, lung structure, and lung function.

Results

Early life arsenic exposure reduced the clearance of and exacerbated the inflammatory response to influenza A, and resulted in acute and long-term changes in lung mechanics and airway structure.

Conclusions

Increased susceptibility to respiratory infections combined with exaggerated inflammatory responses throughout early life may contribute to the development of bronchiectasis in arsenic-exposed populations.

SUBMITTER: Ramsey KA

PROVIDER: S-EPMC3801203 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Publications

Early life arsenic exposure and acute and long-term responses to influenza A infection in mice.

Ramsey Kathryn A KA Foong Rachel E RE Sly Peter D PD Larcombe Alexander N AN Zosky Graeme R GR

Environmental health perspectives 20130822 10

<h4>Background</h4>Arsenic is a significant global environmental health problem. Exposure to arsenic in early life has been shown to increase the rate of respiratory infections during infancy, reduce childhood lung function, and increase the rates of bronchiectasis in early adulthood.<h4>Objective</h4>We aimed to determine if early life exposure to arsenic exacerbates the response to early life influenza infection in mice.<h4>Methods</h4>C57BL/6 mice were exposed to arsenic in utero and througho ...[more]

PMID: 23968752

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Project description:BackgroundSevere acute malnutrition (SAM) in infants may present as one of two distinct syndromic forms: non-edematous (marasmus), with severe wasting and no nutritional edema; or edematous (kwashiorkor) with moderately severe wasting. These differences may be related to developmental changes prior to the exposure to SAM and phenotypic changes appear to persist into adulthood with differences between the two groups. We examined whether the different response to SAM and subsequent trajectories may be explained by developmentally-induced epigenetic differences.MethodsWe extracted genomic DNA from muscle biopsies obtained from adult survivors of kwashiorkor (n=21) or marasmus (n=23) and compared epigenetic profiles (CpG methylation) between the two groups using the Infinium® 450K BeadChip array.FindingsWe found significant differences in methylation of CpG sites from 63 genes in skeletal muscle DNA. Gene ontology studies showed significant differential methylation of genes in immune, body composition, metabolic, musculoskeletal growth, neuronal function and cardiovascular pathways, pathways compatible with the differences in the pathophysiology of adult survivors of SAM.InterpretationThese findings suggest persistent developmental influences on adult physiology in survivors of SAM. Since children who develop marasmus have lower birth weights and after rehabilitation have different intermediary metabolism, these studies provide further support for persistent developmentally-induced phenomena mediated by epigenetic processes affecting both the infant response to acute malnutrition and later life consequences.FundingSupported by a Grant from the Bill and Melinda Gates Foundation (Global Health OPP1066846), Grand Challenge "Discover New Ways to Achieve Healthy Growth."Evidence before this studyPrevious research has shown that infants who develop either kwashiorkor or marasmus in response to SAM differ in birth weight and subsequently have different metabolic patterns in both infancy and adulthood.Added value of this studyThis study demonstrates epigenetic differences in the skeletal muscle of adult survivors of marasmus versus kwashiorkor and these differences are in genes that may underlie the longer-term consequences.Implications of all the available evidenceThese data are compatible with the different clinical responses to SAM arising from developmentally-induced epigenetic changes laid down largely before birth and provide evidence for the predictive adaptive response model operating in human development.

Dataset Information

Early life arsenic exposure and acute and long-term responses to influenza A infection in mice.

Background

Objective

Methods

Results

Conclusions

Publications

Early life arsenic exposure and acute and long-term responses to influenza A infection in mice.

Similar Datasets

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