Changes in human peripheral blood mononuclear cell (HPBMC) populations and T-cell subsets associated with arsenic and polycyclic aromatic hydrocarbon exposures in a Bangladesh cohort.

Fredine T Lauer,Mizanour Rahman,Habibul Ahsan,Xinhua Liu,A K M Rabiul Hasan,Regina M Santella,Nur Alam,Pam Factor-Litvak,Tariqul Islam,Joseph Graziano,Mahbubul Eunus,Faruque Parvez,Scott W Burchiel

doi:10.1371/journal.pone.0220451

Abstract

Exposures to environmental arsenic (As) and polycyclic aromatic hydrocarbons (PAH) have been shown to independently cause dysregulation of immune function. Little data exists on the associations between combined exposures to As and PAH with immunotoxicity in humans. In this work we examined associations between As and PAH exposures with lymphoid cell populations in human peripheral blood mononuclear cells (PBMC), as well as alterations in differentiation and activation of B and T cells. Two hundred men, participating in the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh, were selected for the present study based on their exposure to As from drinking water and their cigarette smoking status. Blood and urine samples were collected from study participants. We utilized multiparameter flow cytometry in PBMC to identify immune cells (B, T, monocytes, NK) as well as the T-helper (Th) cell subsets (Th1, Th2, Th17, and Tregs) following ex vivo activation. We did not find evidence of interactions between As and PAH exposures. However, individual exposures (As or PAH) were associated with changes to immune cell populations, including Th cell subsets. Arsenic exposure was associated with an increase in the percentage of Th cells, and dose dependent changes in monocytes, NKT cells and a monocyte subset. Within the Th cell subset we found that Arsenic exposure was also associated with a significant increase in the percentage of circulating proinflammatory Th17 cells. PAH exposure was associated with changes in T cells, monocytes and T memory (Tmem) cells and with changes in Th, Th1, Th2 and Th17 subsets all of which were non-monotonic (dose dependent). Alterations of immune cell populations caused by environmental exposures to As and PAH may result in adverse health outcomes, such as changes in systemic inflammation, immune suppression, or autoimmunity.

Highlights

Arsenic exposure is prevalent worldwide and occurs primarily through consumption of naturally contaminated ground water and to a lesser degree through food and air
Isolated peripheral blood mononuclear cells (PBMC) include lymphocytes (T, B and natural killer cells (NK) cells) and monocytes; the frequencies of these populations typically range from 79–90% lymphocytes and 10–20% monocytes [36,37,38]
We found associations between urinary arsenic (UAs)/Cr and Th cells (CD3 +CD4+), monocytes (CD14+), non-classical monocytes (CD14+CD16+) and NKT cells (CD3 +CD56+) in models adjusted for age, body mass index (BMI), smoking status and polycyclic aromatic hydrocarbons (PAH)-DNA adducts

Summary

Introduction

Arsenic exposure is prevalent worldwide and occurs primarily through consumption of naturally contaminated ground water and to a lesser degree through food and air. Inorganic arsenite (trivalent, +3) and arsenate (pentavalent, +5) are found in ground water in areas with abundant surrounding natural sources. The Health Effects Arsenic Longitudinal Study (HEALS) cohort, in Araihazar, Bangladesh was established to evaluate the effects of inorganic As exposure on various health outcomes. This cohort of over 35,000 men and women live in rural regions with highly variable concentrations of inorganic As in household well water and are at increased risk of various cancers, diabetes, and cardiovascular and respiratory disease. Increased cardiovascular and pulmonary morbidity has been found in Bangladesh associated with As exposure [4,5,6,7,8,9,10]

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