Two distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide

Abstract

There is growing evidence that plasmacytoid dendritic cells (pDC) are involved in the innate recognition of various microbes. However, the precise consequences of pathogen recognition on pDC activation and function are incompletely understood. Using a novel transgenic mouse model that facilitates the isolation of highly pure pDC populations, we found that influenza virus PR/8, a TLR7 ligand, and CpG 1826 oligonucleotide, a TLR9 ligand, induced surprisingly divergent activation programs in these cells. pDC stimulated with PR/8 produced large amounts of type I IFNs, and CpG 1826-stimulated pDC expressed higher levels of costimulatory molecules and proinflammatory cytokines and induced stronger proliferation of T cells. Transcriptome analysis uncovered the differential regulation in pDC of 178 and 1577 genes by PR/8 and CpG 1826, respectively. These differences may relate to the activation of discrete signaling pathways, as evidenced by distinct ERK1/2 and p38 MAPK phosphorylation kinetics. Finally, pDC isolated ex vivo during PR/8 infection or after i.v. CpG 1826 injection resembled their in vitro counterparts, corroborating that these cells can adopt specialized phenotypes in vivo. Thus, pDC display remarkable functional flexibility, which emphasizes their versatile functions in antimicrobial immunity and inflammatory processes.

Dominant Expression of the Inhibitory FcγRIIB Prevents Antigen Presentation by Murine Plasmacytoid Dendritic Cells

“…Instead, the lack of activating Fc␥R surface expression on murine pDCs is due to the absence of transcriptional expression of all three activating Fc␥Rs ␣-subunits. A recent transcriptional profile of murine splenic pDCs published by an independent group confirms this result (24). The lack of functional activating Fc␥Rs on pDCs in the mouse appears to be generally true across different murine strains, including MRL/Mpj-lpr and (NZB/NZW)F 1 strains genetically susceptible to the development of IC-associated autoimmunity.…”

Concomitant TLR/RLH Signaling of Radioresistant and Radiosensitive Cells Is Essential for Protection against Vesicular Stomatitis Virus Infection

“…Tumor growth was monitored until a maximal diameter of 1.5 cm was reached (38,39). Tumor-bearing mice containing between 10 and 15% Siglec-H + pDC in the spleen were sacrificed, and pDC were isolated from the spleen by negative MACS selection using the Plasmacytoid Dendritic Cell Isolation Kit II (Miltenyi Biotec).…”

“…6A). To address whether in vivodifferentiated pDC similarly conferred protection, WT mice were s.c. treated with 1 3 10 6 Flt3-L-expressing B16 melanoma cells that promoted enhanced development of endogenous pDC (38,39). After 10-14 d, mice developed tumors with a diameter of ∼1.5 cm and carried between 10 and 15% Siglec-H + B220 + pDC in the spleen compared with ,0.1% pDC in untreated mice.…”

Trafficking properties of plasmacytoid dendritic cells in health and disease

“…Exposure of PDCs to HIV-1 surface components triggers the secretion of the CCR5 ligands CCL3 and CCL4, suggesting a role of PDCs in limiting viral spreading [80]. In the lung, PDCs are among the earliest inflammatory cells to enter the bronchoalveolar space following influenza A virus infection [81], and support the recruitment of CXCR3 + and CCR5 + effector T cells through the local secretion of CXCL10 and CCL5 [82]. A protective role for C5a in allergic asthma has been linked to a shift in the MDC/PDCs ratio toward PDCs, with an accompanying decrease in CCL17 production [83].…”