TLR9- and FcεRI-Mediated Responses Oppose One Another in Plasmacytoid Dendritic Cells by Down-Regulating Receptor Expression

Abstract

Plasmacytoid dendritic cells (pDC) express not only TLR9 molecules through which ligation with CpG DNA favors Th1 responses but also possess IgE receptors (FcεRI) implicated in allergen presentation and induction of Th2 responses. This dichotomy prompted an investigation to determine whether TLR9- and IgE receptor-mediated responses oppose one another in pDC by affecting receptor expression and associated functional responses. Results showed that IgE cross-linking reduced TLR9 in pDC and inhibited the capacity of these cells to secrete IFN-α when stimulated with the CpG oligodeoxynucleotide (ODN)-2216. In contrast, an ∼15-fold reduction in FcεRIα mRNA and a loss in surface protein were seen in pDC first exposed to TLR9 ligation with ODN-2216. Results indicated that type I IFNs partly mediated this effect, as rIFN-α also caused a significant ∼4-fold reduction in FcεRIα mRNA. Finally, this reduction in FcεRIα mediated by ODN-2216 correlated with a selective suppression of allergen-induced CD4+ T cell proliferation, but not of responses resulting from tetanus toxoid. Overall, these results imply mechanisms by which specific innate and IgE-dependent immune responses counterregulate one another at the dendritic cell level and may have significant impact on whether an ensuing response is either of Th1 or Th2 in nature.

Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia

“…3 A ). This time course lags behind the onset of expression of Fc RI ␣ which is consistent with reports of Fc RI ␣ ␥ ␥ on human pDCs ( 21 ). This pDC population was distinct from the lung cDC population because Fc RI ␣ -expressing lung cDCs did not express the pDC/B cell marker B220 (Fig.…”

“…In rodents, the highaffi nity IgE receptor has been identifi ed only on mast cells, basophils, and possibly eosinophils ( 19 ). However, in humans, this receptor is also found on skin and peripheral blood cDCs, as well as plasmacytoid DCs (pDCs), albeit as a trimeric form (Fc RI ␣ ␥ ␥ ) that lacks the Fc RI ␤ chain ( 13,20,21 ). Therefore, we questioned whether this form of the receptor might also be found on lung parenchymal cDCs after viral infection.…”

Bacterial c-di-GMP Is an Immunostimulatory Molecule

“…pDCs were prepared, as previously described (29), using a two-step procedure involving Percoll density centrifugation followed with selection for blood DC Ag 4-positive cells (Miltenyi Biotec). The capacity of c-di-GMP to induce IFN-␣ from these cells was assessed using cell culture and ELISA protocols also previously described (29) and was simultaneously compared with the IFN-␣ produced by pDCs in response to cells stimulated with CpG oligodeoxynucleotide (ODN) 2216 (25).…”

Functional changes of dendritic cells in hypersensivity reactions to amoxicillin

“…For pDC, this involved four washes to remove unbound (i.e., BDCA-4 negative) cells and then removal of the column from the magnet and dislodging the pDC by adding buffer. An analysis of pDC suspensions prepared in this manner has previously indicated greater than 95% purity, as determined by BDCA-2 staining (12,14).…”