Maternal third hand exposure to e-cigarette vapor alters lung and bone marrow immune cell responses in offspring in the absence or presence of flu infection

There is increasing evidence that third hand exposure to e-cigarette vapor (e-vapor) can have detrimental effects on the lungs. However, whether maternal exposure during pregnancy results in harmful changes to the offspring is unknown. Using two different e-cigarette settings (low versus high power), BALB/c mice were subjected to third hand e-vapor (e-vapor deposited onto towels, towels changed daily) in the absence or presence of nicotine, before, during, and after pregnancy. Male adult offspring were then infected with mouse-adapted influenza A virus (A/PR/8/34 H1N1) and lung and bone marrow immune cell responses assessed 7 days post infection. Maternal third hand exposure to low power ( M LP) or high power ( M HP) e-vapor with nicotine ( M LP+NIC and M HP+NIC, respectively) increased the percentage of lung immune cells and neutrophils in the bone marrow. Interestingly, Flu-infected offspring from M LP+NIC and M HP+NIC groups had lower percentages of lung alveolar macrophages, and more pronounced increases in neutrophils in the bone marrow, when compared to offspring from M Sham Flu controls. Flu infection also decreased the percentage of lung CD4+ T cells and increased the percentage of lung CD8+ T cells, irrespective of maternal exposure ( M LP−/+NIC and M HP−/+NIC). Significantly, both M LP+NIC and M HP+NIC resulted in blunted activation of lung CD4+ T cells, but only M LP+NIC caused blunted activation of lung CD8+ T cells. Together, we show for the first time that maternal third hand exposure to e-vapor results in significant, long-lived effects on lung and bone marrow immune cell responses in offspring at baseline and in response to Flu infection.