Plasmacytoid dendritic cells regulate host immune response to Citrobacter rodentium induced colitis in colon-draining...

Dendritic cells (DCs) are first in line to sense invading microbes and to deliver signals to other immune cells. Plasmacytoid DCs (pDC) produce high amounts of type I interferons (IFNs) but also regulate immune responses. Using the Clec4C (BDCA2)-diphtheria toxin receptor mouse model allowing conditional pDC depletion, we identified an essential role for pDCs in regulating intestinal inflammation locally in the gut. In pDC-depleted mice, Citrobacter rodentium infection led to enhanced activation of conventional DCs and induction of IFN-γ-producing Th1-cells in colon-draining lymph nodes, while induction of Foxp3⁺ /CD25⁺ Treg and IL-17-producing Th17 cells was impaired. Concomitantly, F4/80⁺ macrophages accumulated into the colon lamina propria in excess, and levels of Il-1β and Tnf transcripts increased and Foxp3⁺ Treg were fewer. Our results indicate that pDCs control inflammation in the gut during C. rodentium infection and that they have an important immune regulatory role in colon-draining lymph nodes.