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 ¼ 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-derivedmacrophage (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 ¼ 0.02) U-As were positively associated with plasma LL-37 levels. Decreased MDM-mediated Spn killing (p ¼ 0.05) and SBA responses (p ¼ 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-1a. 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.

Toxic metal exposure as a possible risk factor for COVID-19 and other respiratory infectious diseases

“…In parallel with impaired lymphocyte functioning, As toxicity is also associated with chronic inflammation and reduced phagocytic receptors—Fcγ and complement receptors (CR) ( Prasad, Sinha, 2017 ). Correspondingly, As exposure was shown to affect innate immunity factors in children ( Parvez et al, 2019 ).…”

Urinary trace elements in association with disease severity and outcome in patients with COVID-19

“…However, the underlying mechanisms needed to be clarified in future studies. Additionally, urinary arsenic levels were seen to be negatively associated with peripheral blood mononuclear cell formation of fractalkine and IL-7, and positively associated with that for IL-13, IL-17 and MIP-1 α in children [ 38 ], suggesting the associations may existed for urinary arsenic with perturbations of inflammatory processes in COVID-19.…”

Exposure to arsenic and level of Vitamin D influence the number of Th17 cells and production of IL-17A in human peripheral blood mononuclear cells in adults

“…However, it is the monomethyl metabolite of arsenite (MMA +3 ) that seems to be responsible for suppression of TCP [ 37 ]. In human studies, As exposure has been associated with alterations in immune function, including suppression of innate and adaptive immunity [ 41 , 42 ], perhaps leading to increased cancer [ 43 ], and increased upper airway infections [ 44 ]. Our studies have shown that As can elevate IL-1β [ 14 ], suggesting that As exposure induces a proinflammatory state.…”