Exposure to low-dose arsenic in early life alters innate immune function in children

Abstract

Early-life exposure to arsenic (As) increases risks of respiratory diseases/infections in children. However, data on the ability of the innate immune system to combat bacterial infections in the respiratory tracts of As-exposed children are scarce. To evaluate whether persistent low-dose As exposure alters innate immune function among children younger than 5 years-of-age, mothers and participating children (N = 51) that were members of the Health Effects of Arsenic Longitudinal Study (HEALS) cohort in rural Bangladesh were recruited. Household water As, past and concurrent maternal urinary As (U-As) as well as child U-As were all measured at enrollment. In addition, U-As metabolites were evaluated. Innate immune function was examined via measures of cathelicidin LL-37 in plasma, ex vivo monocyte-derived-macrophage (MDM)-mediated killing of Streptococcus pneumoniae (Spn), and serum bactericidal antibody (SBA) responses against Haemophilus influenzae type b (Hib). Cyto-/chemokines produced by isolated peripheral blood mononuclear cells (PBMC) were assayed using a Multiplex system. Multivariable linear regression analyses revealed that maternal (p < 0.01) and child (p = 0.02) U-As were positively associated with plasma LL-37 levels. Decreased MDM-mediated Spn killing (p = 0.05) and SBA responses (p = 0.02) were seen to be each associated with fractions of mono-methylarsonic acid (MMA; a U-As metabolite) in the children. In addition, U-As levels were seen to be negatively associated with PBMC formation of fractalkine and IL-7, and positively associated with that for IL-13, IL-17 and MIP-1α. These findings suggested that early-life As exposure may disrupt the innate host defense pathway in these children. It is possible that such disruptions may have health consequences later in life.

Keywords:

• Arsenic
• serum bactericidal antibody response
• macrophage function
• LL-37
• respiratory pathogens

Acknowledgements

The authors would like to thank all the HEALS staff and field-workers for their ongoing commitment to the study.

Disclosure statement

The authors declare no conflicts of interest. The authors alone are responsible for the content of this manuscript.

Additional information

Funding

This work was supported by the funds from University of Chicago and icddr,b. The icddr,b is also grateful to the governments of Bangladesh, Canada, Sweden, and UK for providing core/unrestricted support. Author FP also acknowledges the support of US NIH grants R01 ES019968S1 and R01 ES023888.