Proteomic and Immune Cell Alterations Upon Wildfire Smoke Exposure

Given the increasing prevalence of wildfires worldwide, understanding the effects of wildfire air pollutants on human health, in specific, immunological pathways, is crucial. Exposure to air pollutants has been associated with cardiorespiratory disease, however, immune, and epithelial barrier alterations require further investigation. We aimed to determine the impact of wildfire smoke exposure on the immune system and epithelial barriers, using proteomics and immune cell phenotyping. A cohort from the San Francisco Bay area (n=15; age:30±10y) provided blood samples before (October 2019-March 2020; AQI=37) and during a major wildfire (August 2020; AQI=80). The exposure samples were collected 11 days (range:10-12 days) following continuous exposure to wildfire smoke. We determined temporal alterations in 506 proteins, including zonulin family peptide (ZFP), immune cell phenotypes by mass cytometry (CyTOF), and their interrelationship using a correlation matrix. Targeted proteomic analyses (n=15) revealed a decrease in Spondin-2 and an increase in Granzyme A, B, and H, KIR3DL1, IL-16, Nibrin, PARP-1, C1QTNF-1, FGF-19, and vWF after 11 days in average continuous exposure to a large wildfire smoke (p<0.05). We also observed a large correlation cluster between pathways for immune regulation (IL-16, GZMA, GZMB, GZMH, KIR3DL1), DNA repair (PARP-1, NBN), and NK cells. We did not observe any change in ZFP levels suggesting a change in epithelial barriers. However, ZFP was associated with immune cell phenotypes (Naive CD4+, and Th2 cells). We observed functional changes in critical immune cells and their proteins during wildfire smoke exposure. Future studies should consider immune changes and targets for interventions.