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.
Highlights
Epidemiological studies have shown increased risk of morbidity in children due to chronic and early life arsenic (As) exposure, related to respiratory tract infections (RTI) and diarrheal diseases (Raqib et al 2009; Rahman et al 2017; Sanchez et al 2016)
Serum bactericidal antibody responses and LL-37 levels increased with increasing As exposure, but without any apparent change in macrophage-mediated killing activities
Poor As methylation efficiency was seen to be associated with reduced innate immune function in these children
Summary
Epidemiological studies have shown increased risk of morbidity in children due to chronic and early life arsenic (As) exposure, related to respiratory tract infections (RTI) and diarrheal diseases (Raqib et al 2009; Rahman et al 2017; Sanchez et al 2016). The immunosuppressive effects of As include modulation of the numbers, functions and survival of immune and hematopoietic cells, and impaired humoral and cell-mediated immunity (Dangleben et al 2013; Ferrario et al 2016). The majority of these findings are based on in vitro and experimental studies. Limited information is available on As-induced innate immune modulation in humans, in children
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