Plasmacytoid DCs are gentle guardians of tonsillar epithelium

The outcome of the interaction between plasmacytoid dendritic cells (pDCs) and bacteria has been very controversial: pDCs have been reported not to be activated by extracellular bacteria, to be activated but to only produce TNF-α and IL-6, or to be activated and produce IFN-α, the hallmark of pDC activation, but only if the bacteria have first been opsonized. In this issue of the European Journal of Immunology, Soumelis and colleagues [Eur. J. Immunol. 2013. 43: 1264-1273] unequivocally show that both blood and tonsillar pDCs are fully activated by bacteria and can produce IFN-α. They also show that pDCs are found in the stratified mucosal epithelium in human tonsils, and are "educated" by tonsillar epithelial cells not to release inflammatory cytokines, despite still being capable of activating T cells, albeit with no impact on T-cell polarization. Hence, pDCs can respond to bacteria but can be educated by epithelial cells to remain anergic to potential inflammatory signals. These findings support a mechanism by which intraepithelial pDCs, which are exposed to the microbiota colonizing the upper respiratory tract, remain capable of initiating immunity without overreacting to microbial stimulation.