Proinflammatory polarization of monocytes by particulate air pollutants is mediated by induction of trained immunity in pediatric asthma

Background The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma, are not well understood. We investigated whether ambient levels of fine PM with aerodynamic diameter ≤2.5 microns (PM2.5) are associated with alterations in circulating monocytes in children with or without asthma. Methods Monocyte phenotyping was performed by cytometry time‐of‐flight (CyTOF). Cytokines were measured using cytometric bead array and Luminex assay. ChIP‐Seq was utilized to address histone modifications in monocytes. Results Increased exposure to ambient PM2.5 was linked to specific monocyte subtypes, particularly in children with asthma. Mechanistically, we hypothesized that innate trained immunity is evoked by a primary exposure to fine PM and accounts for an enhanced inflammatory response after secondary stimulation in vitro. We determined that the trained immunity was induced in circulating monocytes by fine particulate pollutants, and it was characterized by the upregulation of proinflammatory mediators, such as TNF, IL‐6, and IL‐8, upon stimulation with house dust mite or lipopolysaccharide. This phenotype was epigenetically controlled by enhanced H3K27ac marks in circulating monocytes. Conclusion The specific alterations of monocytes after ambient pollution exposure suggest a possible prognostic immune signature for pediatric asthma, and pollution‐induced trained immunity may provide a potential therapeutic target for asthmatic children living in areas with increased air pollution. Exposure to air pollutants is associated with the polarization of specific pro‐inflammatory circulating monocytes in children with asthma. Air pollutants induce innate trained immunity in monocytes characterized by the elevation of pro‐inflammatory mediators upon stimulation with house dust mite or LPS. Pollution‐induced trained immunity in monocytes is epigenetically mediated via H3K27ac.Abbreviations: dim., dimension; H3K27ac, acetylation of lysine 27 on histone H3 protein subunit; HDM, house dust mite; IL, interleukin; LPS, lipopolysaccharide; PM2.5, particulate matter with aerodynamic diameter ≤2.5 μm; TNF, tumor necrosis factor; TSS, promoter‐transcription start site; UMAP, Uniform Manifold Approximation and Projection