Wildfire Smoke Inhalation Activates Peripheral Blood Dendritic Cells in Healthy Subjects

Abstract

Wildfire smoke contains inhalable toxic gaseous and particulate matter that is associated with detrimental health effects yet there is no quantifiable outcome of wildfire smoke inhalation on the immune system available. We hypothesized that wildfire smoke exposure activates a dendritic cell response. METHODS: Subject recruitment was coordinated by the clinical trial team of the UC Davis Lung Center. 23 age (18-65 years old) and sex matched healthy subjects were recruited from 2020 Aug 23rd-Sept 3rd (Visit 1), during the peak time of potential smoke exposures from multiple complex fires. Peripheral blood was collected at both visits and processed in an unidentified fashion. Mononuclear cells were isolated by density gradient centrifugation and stained for dendritic cell (DC) membrane markers with fluorescent conjugated antibodies. To study cell activation, multicolor characterization was performed using standard flow cytometric gating strategies (Figure 1 left panel). FACS data was analyzed by FlowJo®. Statistical analysis was performed using Wilcoxon matched-pairs signed rank test (Prism). RESULTS: The wildfires raging around the Sacramento area resulted in a mean AQI (air quality index) of 113 Between 2020 Aug 23rd and Sept 3rd. Although smoke exposure gradually decreased, during the time between visits (the end of Visit 1 and end of Visit 2) there was still an average AQI of 77. All volunteers completed visit 2 and remained healthy. There was no difference in total blood cell count between visits. However, subjects in Visit 1 had a significantly decreased proportion of plasmacytoid Dendritic Cells (pDC) [CD45+ HLA-DR+ CD11c-CD123+] in the circulation, compared to their Visit 2 counts (p=0.004). Meanwhile, the numbers of myeloid lineage conventional type 1 or type 2 Dendritic Cells (cDC1, cDC2) [CD45+ HLA-DR+ CD11c+ CD141+] [CD45+ HLA-DR+ CD11c+ cDC1+ CD16-] did not change significantly. However, wildfire smoke exposure (Visit 1) significantly increased CCR4 (p=0.0002) and CD40 (p=0.01), but not CCR7 expression on cDC2. CONCLUSION: The increase in expression of the chemokine receptor CCR4 suggest increased migration of cDC2 cells to the peripheral tissues. cDC2 cells play a potential role in increased sensitization to allergens and could promote the development of lung disease.