Increased rhinovirus-induced innate immune response in peripheral blood during infancy is associated with improved lung function at school age

Abstract

Exposure to ambient air pollution (AAP) has been associated with exacerbation of asthma, the immune mechanism of which, however, is largely unknown. METHODS: In a cohort of 49 subjects, using single-cell mass cytometry, we characterized and compared immune network changes in peripheral blood mononuclear cells associated with long-term exposure to AAP, asthma, and both, and estimated contributions to these changes from individual air pollutants, measured by a spatial-temporal regression model. RESULTS: Asthma with but not without long-term exposure to AAP is associated with increased proinflammatory CD16 + monocytes and IL-4 production of CD4 + T cells, and decreased B cells and IL-4 and IL-17A production of CD8 + T cells. Tetanus-specific IgG was significantly reduced in subjects with long-term exposure to AAP (p50.02). Seven individual pollutants (O 3 , EC, NO, NO 2 , PM 10 , PM 2.5 , PAH), each correlated with specific sets of immune changes but also shared a common set of changes over short-term (< _6mons) and long-term (>6mons) exposure, including increased na€ ıve T cells, IL-4 production of T cells, and decreased memory T cells. PM 2.5 and NO 2 associated with more immune changes than other pollutants during short-term and long-term exposure, respectively. CONCLUSIONS: Linking single-cell immune profiling with AAP exposure monitoring, we revealed a remodeling of the immune system in asthmatics with long-term exposure to AAP, which is associated with promoted inflammatory monocytes, suppressed type 2 phenotypes of CD8 + T cells, and diminished immunity. We also revealed contributions of individual pollutants to immune network. These results point to new mechanisms and potential new targets for AAP-associated asthma.