Type III IFNs are produced by and stimulate human plasmacytoid dendritic cells.

ABSTRACT: Plasmacytoid dendritic cells (pDC) are rare cells found in peripheral blood and lymphoid tissues. pDC are considered to be "professional" type I IFN-producing cells and produce 10- to 100-fold more IFN-? than other cell types in response to enveloped viruses or synthetic TLR7 and TLR9 agonists. In this study, purified pDC were found to express high levels of IFN-? receptor mRNA, as well as cell-surface IFN-? receptor. We have developed intracellular flow cytometry assays using Abs to IFN-?1/3 or -?2 to assess the expression of IFN-? proteins by pDC. We observed that a subset of human pDC expresses only intracellular IFN-?, whereas another subset produces both IFN-? and IFN-? after stimulation with virus or the TLR9 agonist, CpG A; the cells that coexpressed IFN-? and IFN-? were the cells with the highest levels of IFN-? expression. Ab cross-linking of CD4 or CD303 molecules on pDC inhibited both HSV-induced IFN-? and IFN-? production. Like the production of IFN-?, the HSV-induced IFN-? production in pDC was mediated through TLR9 and independent of virus replication. Exogenous IFN-? treatment of pDC resulted in increased virus-induced expression of both IFN-? and IFN-?. In addition, both exogenous IFN-? and -? inhibited dexamethasone-induced apoptosis of pDC. We conclude that pDC are major producers of IFN-?1 and -?2 in response to viral stimulation and also express functional receptors for this cytokine. Thus, IFN-? can serve as an autocrine signal to strengthen the antiviral response of pDC by increasing IFN-? and IFN-? production, resulting in prolonged pDC survival.

SUBMITTER: Yin Z 

PROVIDER: S-EPMC3579503 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature