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Arsenic and Immune Response to Infection During Pregnancy and Early Life

  • Mechanisms of Toxicity (JR Richardson, Section Editor)
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Abstract

Purpose of Review

Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity—including the specific mechanisms in humans—is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life.

Recent Findings

The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate.

Summary

Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.

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References

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  1. Vahter M. Effects of arsenic on maternal and fetal health. Annu Rev Nutr. 2009;29:381–99.

    Article  CAS  PubMed  Google Scholar 

  2. George CM, et al. Arsenic exposure in drinking water: an unrecognized health threat in Peru. Bull World Health Organ. 2014;92(8):565–72.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Abdul KS, et al. Arsenic and human health effects: a review. Environ Toxicol Pharmacol. 2015;40(3):828–46.

    Article  PubMed  Google Scholar 

  4. Dangleben NL, Skibola CF, Smith MT. Arsenic immunotoxicity: a review. Environ Health. 2013;12:73.

    Article  PubMed  PubMed Central  Google Scholar 

  5. IARC, Arsenic and Arsenic Compounds. 2012

  6. Concha G, Vogler G, Lezcano D, Nermell B, Vahter M. Exposure to inorganic arsenic metabolites during early human development. Toxicol Sci. 1998;44:185–90.

    Article  CAS  PubMed  Google Scholar 

  7. Dietert RR. Developmental immunotoxicity, perinatal programming, and noncommunicable diseases: focus on human studies. Adv Med. 2014;2014:867805.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Diamond MP, Gabriele R. Effects of pregnancy on metabolism. Comprehensive physiology. Hoboken: John Wiley & Sons, Inc.; 2011.

    Google Scholar 

  9. Mor G, Cardenas I. The immune system in pregnancy: a unique complexity. Am J Reprod Immunol. 2010;63(6):425–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Lantz RC, et al. Effect of arsenic exposure on alveolar macrophage function. I. Effect of soluble As(III) and As(V). Environ Res. 1994;67(2):183–95.

    Article  CAS  PubMed  Google Scholar 

  11. Banerjee N, et al. Chronic arsenic exposure impairs macrophage functions in the exposed individuals. J Clin Immunol. 2009;29(5):582–94.

    Article  CAS  PubMed  Google Scholar 

  12. Biswas R, et al. Analysis of T-cell proliferation and cytokine secretion in the individuals exposed to arsenic. Hum Exp Toxicol. 2008;27(5):381–6.

    Article  CAS  PubMed  Google Scholar 

  13. Hernandez-Castro B, et al. Effect of arsenic on regulatory T cells. J Clin Immunol. 2009;29(4):461–9.

    Article  CAS  PubMed  Google Scholar 

  14. Soto-Pena GA, Vega L. Arsenic interferes with the signaling transduction pathway of T cell receptor activation by increasing basal and induced phosphorylation of Lck and Fyn in spleen cells. Toxicol Appl Pharmacol. 2008;230(2):216–26.

    Article  CAS  PubMed  Google Scholar 

  15. Sikorski EE, et al. Immunotoxicity of the semiconductor gallium arsenide in female B6C3F1 mice. Fundam Appl Toxicol. 1989;13(4):843–58.

    Article  CAS  PubMed  Google Scholar 

  16. Lemarie A, et al. Human macrophages constitute targets for immunotoxic inorganic arsenic. J Immunol. 2006;177(5):3019–27.

    Article  CAS  PubMed  Google Scholar 

  17. Soto-Pena GA, et al. Assessment of lymphocyte subpopulations and cytokine secretion in children exposed to arsenic. FASEB J. 2006;20(6):779–81.

    CAS  PubMed  Google Scholar 

  18. • Ahmed S, et al. Arsenic exposure and cell-mediated immunity in pre-school children in rural Bangladesh. Toxicol Sci. 2014;141(1):166–75. In this MINIMat substudy, authors use data collected prospectively from pregnant mothers and their children to associate recent and prenatal arsenic exposure with T cell-mediated immunologic memory.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Blakley BR, Sisodia CS, Mukkur TK. The effect of methylmercury, tetraethyl lead, and sodium arsenite on the humoral immune response in mice. Toxicol Appl Pharmacol. 1980;52(2):245–54.

    Article  CAS  PubMed  Google Scholar 

  20. Islam LN, et al. Association of respiratory complications and elevated serum immunoglobulins with drinking water arsenic toxicity in human. J Environ Sci Health A Tox Hazard Subst Environ Eng. 2007;42(12):1807–14.

    Article  CAS  PubMed  Google Scholar 

  21. Ser, P.H., et al., Arsenic exposure increases maternal but not cord serum IgG in Bangladesh. Pediatr Int. 2014;57(1):119–125.

  22. Nain S, Smits JE. Pathological, immunological and biochemical markers of subchronic arsenic toxicity in rats. Environ Toxicol. 2012;27(4):244–54.

    Article  CAS  PubMed  Google Scholar 

  23. Patra PH, et al. Immunotoxic and genotoxic potential of arsenic and its chemical species in goats. Toxicol Int. 2013;20(1):6–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Saha A, et al. Vaccine specific immune response to an inactivated oral cholera vaccine and EPI vaccines in a high and low arsenic area in Bangladeshi children. Vaccine. 2013;31(4):647–52.

    Article  CAS  PubMed  Google Scholar 

  25. Farzan SF, et al. In utero arsenic exposure and infant infection in a United States cohort: a prospective study. Environ Res. 2013;126:24–30.

    Article  CAS  PubMed  Google Scholar 

  26. Kile ML, et al. A prospective cohort study of the association between drinking water arsenic exposure and self-reported maternal health symptoms during pregnancy in Bangladesh. Environ Health. 2014;13(1):29.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Dangleben NL, Skibola CF, Smith MT. Arsenic immunotoxicity: a review. Environ Health. 2013;12(1):73.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Rahman A, et al. Arsenic exposure in pregnancy increases the risk of lower respiratory tract infection and diarrhea during infancy in Bangladesh. Environ Health Perspect. 2011;119(5):719–24.

    Article  CAS  PubMed  Google Scholar 

  29. •• Ramsey KA, et al. Early life arsenic exposure and acute and long-term responses to influenza A infection in mice. Environ Health Perspect. 2013;121(10):1187–93. This study outlines an in vivo model of prenatal arsenic exposure and neonatal immune challenge.

    PubMed  PubMed Central  Google Scholar 

  30. Raqib R, et al. Effects of in utero arsenic exposure on child immunity and morbidity in rural Bangladesh. Toxicol Lett. 2009;185(3):197–202.

    Article  CAS  PubMed  Google Scholar 

  31. •• Heaney CD, et al. Arsenic exposure and hepatitis E virus infection during pregnancy. Environ Res. 2015;142:273–80. This study provides an example of a prospective cohort study assessing the immunotoxic effects of arsenic exposure during the pregnancy and postpartum periods.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Smith AH, et al. Evidence from Chile that arsenic in drinking water may increase mortality from pulmonary tuberculosis. Am J Epidemiol. 2011;173(4):414–20.

    Article  PubMed  Google Scholar 

  33. Murphy KTP, Walport M. Immunobiology. Seventh ed. New York: Garland Science, Taylor & Francis Group, LLC; 2008.

    Google Scholar 

  34. Brambell FW. The transmission of immunity from mother to young and the catabolism of immunoglobulins. Lancet. 1966;2(7473):1087–93.

    Article  CAS  PubMed  Google Scholar 

  35. Palmeira P, et al. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol. 2012;2012:985646.

    Article  PubMed  Google Scholar 

  36. Gendrel D, et al. Placental transfer of tetanus antibodies and protection of the newborn. J Trop Pediatr. 1990;36(6):279–82.

    Article  CAS  PubMed  Google Scholar 

  37. Hartter HK, et al. Placental transfer and decay of maternally acquired antimeasles antibodies in Nigerian children. Pediatr Infect Dis J. 2000;19(7):635–41.

    Article  CAS  PubMed  Google Scholar 

  38. Goncalves G, et al. Transplacental transfer of measles and total IgG. Epidemiol Infect. 1999;122(2):273–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Silveira Lessa AL, et al. Preterm and term neonates transplacentally acquire IgG antibodies specific to LPS from Klebsiella pneumoniae, Escherichia coli and Pseudomonas aeruginosa. FEMS Immunol Med Microbiol. 2011;62(2):236–43.

    Article  PubMed  Google Scholar 

  40. Islam LN, et al. Function of serum complement in drinking water arsenic toxicity. J Toxicol. 2012;2012:302817.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Cardenas A, et al. Arsenic exposure and prevalence of the varicella zoster virus in the United States: NHANES (2003-2004 and 2009-2010). Environ Health Perspect. 2015;123(6):590–6.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Cardenas A, et al. Arsenic exposure and the seroprevalence of total hepatitis A antibodies in the US population: NHANES, 2003-2012. Epidemiol Infect. 2016;144(8):1641–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Martin-Chouly C, et al. Inorganic arsenic alters expression of immune and stress response genes in activated primary human T lymphocytes. Mol Immunol. 2011;48(6–7):956–65.

    Article  CAS  PubMed  Google Scholar 

  44. Conde P, et al. Sodium arsenite-induced inhibition of cell proliferation is related to inhibition of IL-2 mRNA expression in mouse activated T cells. Arch Toxicol. 2007;81(4):251–9.

    Article  CAS  PubMed  Google Scholar 

  45. Galicia G, et al. Sodium arsenite retards proliferation of PHA-activated T cells by delaying the production and secretion of IL-2. Int Immunopharmacol. 2003;3(5):671–82.

    Article  CAS  PubMed  Google Scholar 

  46. Tenorio EP, Saavedra R. Differential effect of sodium arsenite during the activation of human CD4+ and CD8+ T lymphocytes. Int Immunopharmacol. 2005;5(13–14):1853–69.

    Article  CAS  PubMed  Google Scholar 

  47. Vega L, et al. Sodium arsenite reduces proliferation of human activated T-cells by inhibition of the secretion of interleukin-2. Immunopharmacol Immunotoxicol. 1999;21(2):203–20.

    Article  CAS  PubMed  Google Scholar 

  48. Vega L, et al. Helper T cell subpopulations from women are more susceptible to the toxic effect of sodium arsenite in vitro. Toxicology. 2004;199(2–3):121–8.

    Article  CAS  PubMed  Google Scholar 

  49. Mozdzanowska K, et al. Roles of CD4+ T-cell-independent and -dependent antibody responses in the control of influenza virus infection: evidence for noncognate CD4+ T-cell activities that enhance the therapeutic activity of antiviral antibodies. J Virol. 2005;79(10):5943–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Akao Y, et al. Arsenic induces apoptosis in B-cell leukaemic cell lines in vitro: activation of caspases and down-regulation of Bcl-2 protein. Br J Haematol. 1998;102(4):1055–60.

    Article  CAS  PubMed  Google Scholar 

  51. Burchiel SW, et al. Differential susceptibility of human peripheral blood T cells to suppression by environmental levels of sodium arsenite and monomethylarsonous acid. PLoS One. 2014;9(10):e109192.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Ahmed S, et al. In utero arsenic exposure is associated with impaired thymic function in newborns possibly via oxidative stress and apoptosis. Toxicol Sci. 2012;129(2):305–14.

    Article  CAS  PubMed  Google Scholar 

  53. Nadeau, K.C., et al., In utero arsenic exposure and fetal immune repertoire in a US pregnancy cohort. Clin Immunol. 2014;155(2):188–197.

  54. Kile ML, et al. Effect of prenatal arsenic exposure on DNA methylation and leukocyte subpopulations in cord blood. Epigenetics. 2014;9(5):774–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. NCBI, CD151 CD151 molecule (Raph Blood Group) [Homo sapiens (humans)]. 2016.

  56. Bailey KA, et al. Prenatal arsenic exposure and shifts in the newborn proteome: interindividual differences in tumor necrosis factor (TNF)-responsive signaling. Toxicol Sci. 2014;139(2):328–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Heck JE, et al. Risk of leukemia in relation to exposure to ambient air toxics in pregnancy and early childhood. Int J Hyg Environ Health. 2014;217(6):662–8.

    Article  CAS  PubMed  Google Scholar 

  58. Xu HM, Medina S, Lauer FT, Douillet C, Liu KJ, Hudson LG, Styblo M, Burchiel SW. Differential sensitivities of bone marrow, spleen and thymus to genotoxicity induced by environmentally relevant concentrations of arsenite. Toxicol Lett. 2016;262:55–61.

    Article  CAS  PubMed  Google Scholar 

  59. Patterson R, et al. Arsenic-induced alterations in the contact hypersensitivity response in Balb/c mice. Toxicol Appl Pharmacol. 2004;198(3):434–43.

    Article  CAS  PubMed  Google Scholar 

  60. Kozul CD, et al. Low-dose arsenic compromises the immune response to influenza a infection in vivo. Environ Health Perspect. 2009;117(9):1441–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Goytia-Acevedo RC, Cebrian ME, Calderon-Aranda ES. Differential effects of arsenic on intracellular free calcium levels and the proliferative response of murine mitogen-stimulated lymphocytes. Toxicology. 2003;189(3):235–44.

    Article  CAS  PubMed  Google Scholar 

  62. Cho Y, et al. Age-related effects of sodium arsenite on splenocyte proliferation and Th1/Th2 cytokine production. Arch Pharm Res. 2012;35(2):375–82.

    Article  CAS  PubMed  Google Scholar 

  63. • Xu H, et al. Environmentally relevant concentrations of arsenite and monomethylarsonous acid inhibit IL-7/STAT5 cytokine signaling pathways in mouse CD3+CD4-CD8- double negative thymus cells. Toxicol Lett. 2016;247:62–8. This recent article provides novel insight into the potential immune signaling cascades responsible for arsenic-induced immunotoxicity.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Ezeh PC, et al. Monomethylarsonous acid (MMA+3) inhibits IL-7 signaling in mouse pre-B cells. Toxicol Sci. 2016;149(2):289–99.

    Article  CAS  PubMed  Google Scholar 

  65. Ramsey KA, et al. In utero exposure to arsenic alters lung development and genes related to immune and mucociliary function in mice. Environ Health Perspect. 2013;121(2):244–50.

    PubMed  Google Scholar 

  66. Smith AH, et al. Chronic respiratory symptoms in children following in utero and early life exposure to arsenic in drinking water in Bangladesh. Int J Epidemiol. 2013;42(4):1077–86.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Mazumder DNG, et al. Bronchiectasis in persons with skin lesions resulting from arsenic in drinking water. Epidemiology. 2005;16(6):760–5.

    Article  PubMed  Google Scholar 

  68. Burggren WW, Mueller CA. Developmental critical windows and sensitive periods as three-dimensional constructs in time and space. Physiol Biochem Zool. 2015;88(2):91–102.

    Article  PubMed  Google Scholar 

  69. De Boo HA, Harding JE. The developmental origins of adult disease (Barker) hypothesis. Australian and New Zealand Journal of Obstetrics and Gynaecolog. 2006;46:4–14.

    Article  Google Scholar 

  70. Okae H, et al. Genome-wide analysis of DNA methylation dynamics during early human development. PLoS Genet. 2014;10(12):e1004868.

    Article  PubMed  PubMed Central  Google Scholar 

  71. Skogen JC, Overland S. The fetal origins of adult disease: a narrative review of the epidemiological literature. JRSM Short Rep. 2012;3(8):59.

    Article  PubMed  PubMed Central  Google Scholar 

  72. Grandjean P, Andersen EW, Budtz-Jørgensen E, Nielsen F, Mølbak K, Weihe P, Heilmann C. Serum vaccine antibody concentrations in children exposed to perfluorinated compounds. JAMA. 2012;307(4):391–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Heilmann C, et al. Reduced antibody responses to vaccinations in children exposed to polychlorinated biphenyls. PLoS Med. 2006;3(8):e311.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Heilmann C, Budtz-Jørgensen E, Nielsen F, Heinzow B, Weihe P, Grandjean P. Serum concentrations of antibodies against vaccine toxoids in children exposed perinatally to immunotoxicants. Environ Health Perspect. 2010;118(10):1434–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Jusko TA, et al. A birth cohort study of maternal and infant serum PCB-153 and DDE concentrations and responses to infant tuberculosis vaccination. Environ Health Perspect. 2016;124(6):813–21.

    PubMed  Google Scholar 

  76. Kraus TA, et al. Characterizing the pregnancy immune phenotype: results of the viral immunity and pregnancy (VIP) study. J Clin Immunol. 2012;32(2):300–11.

    Article  CAS  PubMed  Google Scholar 

  77. CDC, Flu Vaccine Safety and Pregnancy. 2016

  78. CDC, Immunization Schedule: Child and Adolescent Schedule. 2016

  79. Ser PH, et al. Arsenic exposure increases maternal but not cord serum IgG in Bangladesh. Pediatr Int. 2015;57(1):119–25.

    Article  CAS  PubMed  Google Scholar 

  80. Howe CG, et al. Folate and cobalamin modify associations between S-adenosylmethionine and methylated arsenic metabolites in arsenic-exposed Bangladeshi adults. J Nutr. 2014;144(5):690–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hall MN, et al. Folate, cobalamin, cysteine, homocysteine, and arsenic metabolism among children in Bangladesh. Environ Health Perspect. 2009;117(5):825–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hall M, et al. Determinants of arsenic metabolism: blood arsenic metabolites, plasma folate, cobalamin, and homocysteine concentrations in maternal-newborn pairs. Environ Health Perspect. 2007;115(10):1503–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Petrick JS, et al. Inorganic arsenic as a developmental toxicant: in utero exposure and alterations in the developing rat lungs. Mol Nutr Food Res. 2009;53(5):583–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Environmental Health and Engineering, Johns Hopkins Bloomberg School of Public Health, Room W7033B, 615 North Wolfe Street, Baltimore, MD, 21205, USA

    Sarah E. Attreed, Ana Navas-Acien & Christopher D. Heaney

  2. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Ana Navas-Acien & Christopher D. Heaney

  3. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA

    Ana Navas-Acien

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  1. Sarah E. Attreed
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  2. Ana Navas-Acien
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  3. Christopher D. Heaney
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Correspondence to Christopher D. Heaney.

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The authors declare that they have no conflict of interest.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

Funding Sources

The authors would like to acknowledge their funding sources: NIH grants 1R01ES026973-01A1, R01ES021367, and R01ES025216.

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This article is part of the Topical Collection on Mechanisms of Toxicity

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Attreed, S.E., Navas-Acien, A. & Heaney, C.D. Arsenic and Immune Response to Infection During Pregnancy and Early Life. Curr Envir Health Rpt 4, 229–243 (2017). https://doi.org/10.1007/s40572-017-0141-4

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