Arsenic Exposure and Immunotoxicity: a Review Including the Possible Influence of Age and Sex

Ferrario, Daniele; Gribaldo, Laura; Hartung, Thomas

doi:10.1007/s40572-016-0082-3

Cited by 93 publications

(53 citation statements)

References 130 publications

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“…The observed inverse associations between exposure and infection resistance have been supported by mechanistic and animal studies [9–12]. Although most of these studies were conducted in populations exposed to high levels of arsenic, our group has recently reported increased susceptibility to infections in those exposed to chronic levels of low to intermediate exposure levels of arsenic [13, 14].…”

Section: Introductionmentioning

confidence: 77%

Cord blood T cell subpopulations and associations with maternal cadmium and arsenic exposures

Nygaard

Palys

et al. 2017

PLoS ONE

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BackgroundArsenic and cadmium are environmental pollutants, and although the evidence for adverse immune effects after prenatal arsenic and cadmium exposures is increasing, little is known about the underlying immunological mechanisms.MethodsWe investigated the relationship between prenatal arsenic and cadmium exposures and a variety of T cell subpopulations measured in cord blood for 63 participants in the New Hampshire Birth Cohort Study. Post-partum toenail concentrations of arsenic and cadmium were used as an estimate of maternal exposure during pregnancy. The characteristics of cord blood proportions of T lymphocytes and subpopulations (expression of markers for Th1, Th2, Th17, Th1Th17, induced and natural regulatory T cells and NKTs) are presented.ResultsIn regression analyses, maternal arsenic exposure levels were inversely associated with cord blood T helper memory cells (-21%, 95% CI: -36%, -3%) and the association was found to be stronger in females. They were also inversely associated with activated T helper memory cells, particularly in males (-26%, 95% CI: -43%, -3%). Similarly, inverse associations were observed between cadmium exposure levels and activated T helper memory cells (-16%, 95% CI: -30%, -1%) and also for T helper memory cells in females (-20%, 95% CI: -35%, -3%).ConclusionThe results suggest that prenatal exposures to relatively low levels of arsenic and cadmium may contribute to altered distribution of T cell populations at birth. These changes in theory, could have contributed to the previously reported immunosuppressive effects observed later in infancy/childhood.

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Section: Introductionmentioning

confidence: 77%

Cord blood T cell subpopulations and associations with maternal cadmium and arsenic exposures

Nygaard

Palys

et al. 2017

PLoS ONE

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“…A broad range of industrial and environmental chemicals have been suggested to target the immune system . The increased occurrence of immune‐related diseases in recent decades can in part be traced back to the resultant disruption of immune functions .…”

Section: Introductionmentioning

confidence: 99%

Cis -bifenthrin induces immunotoxicity in adolescent male C57BL/6 mice

Wang

Gao

et al. 2017

Environmental Toxicology

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Bifenthrin (BF) is an important synthetic pyrethroid. Previous studies have demonstrated that cis-BF exhibits toxic effects on development, the neurological, reproductive and endocrine system. In this study, we evaluated the immunotoxicity caused by cis-BF in adolescent male C57BL/6 mice. Mice were exposed orally to 0, 5, 10, and 20 mg/kg/d for 3 weeks. The results showed that body weight, spleen weight, and splenic cellularity decreased in mice exposed to 20 mg/kg/d cis-BF. Additionally, we found that the mRNA levels of the pro-inflammatory factors IL-1β, IL-6, CXCL-1, and TNF-α, in peritoneal macrophages, the spleen, and the thymus were inhibited in the cis-BF-treated groups. Moreover, MTT assays demonstrated that cis-BF inhibited splenocyte proliferation stimulated by LPS or Con A, as well as the secretion of IFN-γ on Con A stimulation. Collectively, the results of this study suggest that exposure to cis-BF has the potential to induce immunotoxicity in adolescent male C57BL/6 mice.

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“…The mechanisms behind the immunotoxic effects of arsenic remain unclear (Ahmed et al 2014; Ferrario et al 2016). One potential mechanism is that arsenic could interfere with the expression of immune-related genes.…”

Section: Introductionmentioning

confidence: 99%

Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women

et al. 2016

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Arsenic, a carcinogen with immunotoxic effects, is a common contaminant of drinking water and certain food worldwide. We hypothesized that chronic arsenic exposure alters gene expression, potentially by altering DNA methylation of genes encoding central components of the immune system. We therefore analyzed the transcriptomes (by RNA sequencing) and methylomes (by target-enrichment next-generation sequencing) of primary CD4-positive T cells from matched groups of four women each in the Argentinean Andes, with fivefold differences in urinary arsenic concentrations (median concentrations of urinary arsenic in the lower- and high-arsenic groups: 65 and 276 μg/l, respectively). Arsenic exposure was associated with genome-wide alterations of gene expression; principal component analysis indicated that the exposure explained 53% of the variance in gene expression among the top variable genes and 19% of 28,351 genes were differentially expressed (false discovery rate <0.05) between the exposure groups. Key genes regulating the immune system, such as tumor necrosis factor alpha and interferon gamma, as well as genes related to the NF-kappa-beta complex, were significantly downregulated in the high-arsenic group. Arsenic exposure was associated with genome-wide DNA methylation; the high-arsenic group had 3% points higher genome-wide full methylation (>80% methylation) than the lower-arsenic group. Differentially methylated regions that were hyper-methylated in the high-arsenic group showed enrichment for immune-related gene ontologies that constitute the basic functions of CD4-positive T cells, such as isotype switching and lymphocyte activation and differentiation. In conclusion, chronic arsenic exposure from drinking water was related to changes in the transcriptome and methylome of CD4-positive T cells, both genome wide and in specific genes, supporting the hypothesis that arsenic causes immunotoxicity by interfering with gene expression and regulation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00204-016-1879-4) contains supplementary material, which is available to authorized users.

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Arsenic Exposure and Immunotoxicity: a Review Including the Possible Influence of Age and Sex

Cited by 93 publications

References 130 publications

Cord blood T cell subpopulations and associations with maternal cadmium and arsenic exposures

Cord blood T cell subpopulations and associations with maternal cadmium and arsenic exposures

Cis -bifenthrin induces immunotoxicity in adolescent male C57BL/6 mice

Transcriptomics and methylomics of CD4-positive T cells in arsenic-exposed women

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