Transitional dendritic cells are distinct from conventional DC2 precursors and mediate proinflammatory antiviral responses

Establishment of antiviral immune responses depends on dendritic cells (DCs), but how transitional DCs compare with other DC subsets in this regard is unclear. Here the authors show the origins of these cells and their proinflammatory function during viral infection. High-dimensional approaches have revealed heterogeneity amongst dendritic cells (DCs), including a population of transitional DCs (tDCs) in mice and humans. However, the origin and relationship of tDCs to other DC subsets has been unclear. Here we show that tDCs are distinct from other well-characterized DCs and conventional DC precursors (pre-cDCs). We demonstrate that tDCs originate from bone marrow progenitors shared with plasmacytoid DCs (pDCs). In the periphery, tDCs contribute to the pool of ESAM(+) type 2 DCs (DC2s), and these DC2s have pDC-related developmental features. Different from pre-cDCs, tDCs have less turnover, capture antigen, respond to stimuli and activate antigen-specific naive T cells, all characteristics of differentiated DCs. Different from pDCs, viral sensing by tDCs results in IL-1 & beta; secretion and fatal immune pathology in a murine coronavirus model. Our findings suggest that tDCs are a distinct pDC-related subset with a DC2 differentiation potential and unique proinflammatory function during viral infections.

Automated summary

This study investigates the role of transitional dendritic cells (tDCs) in antiviral immune responses and reveals their distinct features compared to other dendritic cell subsets. The authors show that tDCs share bone marrow progenitors with plasmacytoid DCs (pDCs) and contribute to the development of ESAM(+) type 2 DCs (DC2s). Unlike other DC subsets, tDCs exhibit characteristics of differentiated DCs, including antigen capture, response to stimuli, and activation of antigen-specific naive T cells. Moreover, viral sensing by tDCs leads to IL-1β secretion and fatal immune pathology. Overall, tDCs are a unique pDC-related subset with a DC2 differentiation potential and a special proinflammatory function during viral infections.