Transition metal containing particulate matter promotes th1 and th17 inflammatory response by monocyte activation in organic and inorganic compounds dependent manner

Abstract

In recent years, a significant increase in the frequency of disorders caused by air pollutants has been observed. Here we asked whether transition metal-containing particulate matter (TMCPM), a component of air pollution, has an effect on the activity of human CD4+ T cell subsets (Th1, Th2, Th17, and Treg). Peripheral blood mononuclear cells (PBMC) from healthy donors were cultured with or without NIST (SRM 1648a—standard urban particulate matter purchased from the National Institute for Standards and Technology) and LAP (SRM 1648a particulate matter treated within 120 min with cold oxygen plasma) preparations of TMCPM, differing in organic compounds content. Data show that TMCPM treatment increased the level of CD4+ cells positive for IFN-γ and IL-17A, specific for Th1 and Th17 cells, respectively. Moreover, a substantial decrease in frequency of Foxp3 positive CD4+ cells was observed in parallel. This effect was more pronounced for NIST particles, containing more organic components, including endotoxin (LPS-lipopolysaccharide) and required the presence of monocytes. Inactivation of LPS by treatment of TMCPM with polymyxin B reduced the inflammatory response of monocytes and Th subsets but did not abolish this activity, suggesting a role of their inorganic components. In conclusion, treatment of human PBMC with TMCPM skews the balance of Th1/Th2 and Treg/Th17 cells, promoting polarization of CD4+ T cells into Th1 and Th17 subsets. This phenomenon requires activation of monocytes and depends on the organic and inorganic fractions, including endotoxin content in TMCPM, as significantly higher inflammatory response was observed for the NIST comparing to LAP. This observation may shed a new light on the role of TMCPM in development and exacerbation of allergies, inflammatory, and autoimmune disorders.