Sampling and signaling in plasmacytoid dendritic cells: the potential roles of Siglec-H

Plasmacytoid dendritic cells (pDCs) detect viruses through toll-like receptor (TLR)7 and TLR9 and respond by secreting type I interferons (IFNs). Because TLR7 and TLR9 are present in endosomes, a mechanism is required to capture and deliver viruses to TLRs. A member of the sialic acid binding Ig-like lectin (Siglec) family, Siglec-H, has recently been identified as a specific surface marker for pDCs in mice. Siglec-H is endocytosed and can mediate the uptake of antigens for processing and presentation. Thus, Siglec-H might have a role in the capture of viruses or other pathogens for their delivery to intracellular TLRs. Paradoxically, Siglec-H also transmits intracellular signals through the associated adaptor DAP12, which reduces pDC responses to TLR ligands. In this review, we discuss models to explain the potential outcomes of Siglec-H engagement in the pDC secretion of type I IFN.