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

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.

Arsenic exposure associated T cell proliferation, smoking, and vitamin D in Bangladeshi men and women

“…Various measures of adaptive immunity [7,10,[18][19][20][21] and innate immunity [22][23][24] are suppressed by arsenic exposure. TCP is critical for cell activation, effector, and helper cell functions [25].…”

“…Hematology tests, such as full blood count and blood glucose levels were conducted. Twenty-five individuals were excluded due to: abnormal blood sugar levels (8), suffering from urinary tract infection (9) or lymphocytosis (2). Furthermore, three samples were excluded at time of PBMC isolation due to hemolysis and another three for low cell count and low viability.…”

“…Urine samples (15 ml) were collected at the study clinic at Araihazar, Bangladesh. Total arsenic in urine was accessed by graphite furnace atomic-absorption spectrophotometry (GFAAS) as previously described [7,8]. Urinary creatinine, quantified by a colorimetric method based on the Jaffe reaction, was used to correct urinary arsenic (UAs) and metabolites.…”

“…Previous work from our labs has shown that arsenic modulates various immune functions measured in cryopreserved peripheral blood mononuclear cells (PBMC) obtained from men chronically exposed to arsenic in Bangladesh [7,8]. Those studies were limited to 181 males equally divided between smokers and never smokers as well as low and high arsenic exposure.…”

The regulatory role of peripheral blood mononuclear cell function by A20

“…Peripheral blood mononuclear cells (PBMCs) are immune cells including lymphocytes (T cells, B cells, natural killer cells), monocytes and dendritic cells, which play important roles in initiating and regulating immunity against pathogens or immune tolerance to allergens (Lauer et al, 2019;Simader et al, 2019). Activation of PBMCs is induced upon exposure to multiple stimuli by the binding with tolllike receptors (TLRs), recognition elements of the innate immune system (Simader et al, 2019).…”