Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA.
Infectious Diseases Division, icddr,b, Dhaka, Bangladesh.
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 ( = 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, monocyte-derived-macrophage (MDM)-mediated killing of (), and serum bactericidal antibody (SBA) responses against type b (). Cyto-/chemokines produced by isolated peripheral blood mononuclear cells (PBMC) were assayed using a Multiplex system. Multivariable linear regression analyses revealed that maternal ( < 0.01) and child ( = 0.02) U-As were positively associated with plasma LL-37 levels. Decreased MDM-mediated killing ( = 0.05) and SBA responses ( = 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.
儿童早期砷（As）暴露会增加患呼吸道疾病/感染的风险。然而，关于暴露于 As 的儿童呼吸道固有免疫系统抵抗细菌感染能力的数据却很少。为了评估持续低剂量 As 暴露是否会改变 5 岁以下儿童的固有免疫功能，招募了孟加拉国农村健康影响砷纵向研究（HEALS）队列的母亲和参与儿童（ = 51）。在入组时，均测量了家庭用水 As、过去和当前的母体尿砷（U-As）以及儿童 U-As。此外，还评估了 U-As 的代谢产物。通过血浆中抗菌肽 LL-37 的测量、单核细胞衍生的巨噬细胞（MDM）对金黄色葡萄球菌的杀伤作用（）以及针对 b 型（）的血清杀菌抗体（SBA）反应来检查固有免疫功能。使用多聚酶链式反应系统检测分离的外周血单核细胞（PBMC）中产生的细胞因子/趋化因子。多变量线性回归分析显示，母体（ < 0.01）和儿童（ = 0.02）U-As 与血浆 LL-37 水平呈正相关。MDM 介导的 杀伤（ = 0.05）和 SBA 反应（ = 0.02）的减少分别与儿童中一甲基砷酸（MMA；U-As 的一种代谢产物）的分数相关。此外，U-As 水平与 PBMC 形成 fractalkine 和 IL-7 的减少呈负相关，与 IL-13、IL-17 和 MIP-1α 的形成呈正相关。这些发现表明，儿童早期 As 暴露可能会破坏这些儿童的固有宿主防御途径。这种破坏可能会对以后的生活产生健康后果。
