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

J Immunotoxicol. 2019 Dec;16(1):201-209. doi: 10.1080/1547691X.2019.1657993.


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; LL-37; macrophage function; respiratory pathogens; serum bactericidal antibody response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Antibodies, Bacterial / immunology
  • Arsenic / toxicity*
  • Bangladesh
  • Child, Preschool
  • Environmental Exposure / adverse effects*
  • Female
  • Humans
  • Immunity, Innate / drug effects*
  • Longitudinal Studies
  • Macrophages / immunology*
  • Macrophages / pathology
  • Male
  • Monocytes / immunology*
  • Monocytes / pathology
  • Rural Population*
  • Streptococcus pneumoniae / immunology


  • Antibodies, Bacterial
  • Arsenic