BCG vaccination induces enhanced frequencies of dendritic cells and altered plasma levels of type I and type III interferons in elderly individuals

•BCG vaccination induces significantly enhanced frequencies of DC subsets•BCG vaccination induces diminished plasma levels of type I interferons but increased levels of type III interferons•BCG vaccination can potentially boost immune responses in a non -specific or off-target manner in elderly individuals. BCG can improve the response to vaccines directed against viral infections, and also, BCG vaccination reduces all-cause mortality, most likely by protecting against unrelated infections. However, the effect of BCG vaccination on dendritic cell (DC) subsets is not well characterized. We investigated the impact of BCG vaccination on the frequencies of DC subsets and type I and III interferons (IFNs) using whole blood and plasma samples in a group of elderly individuals (age 60-80 years) at one-month post-vaccination as part of our clinical study to examine the effect of BCG on COVID-19. Our results demonstrate that BCG vaccination induced enhanced frequencies of plasmacytoid DC (pDC) and myeloid DC (mDC). BCG vaccination also induced diminished plasma levels of type I IFNs, IFNα and IFNβ but increased levels of type III IFNs, IL-28A and IL-29. Thus, BCG vaccination was associated with enhanced DC subsets and IL-28A/IL-29 in elderly individuals, suggesting its ability to induce non-specific innate immune responses.