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

Authors
  • Yin, Zhiwei
  • Dai, Jihong
  • Deng, Jing
  • Sheikh, Faruk
  • Natalia, Mahwish
  • Shih, Tiffany
  • Lewis-Antes, Anita
  • Amrute, Sheela B
  • Garrigues, Ursula
  • Doyle, Sean
  • Donnelly, Raymond P
  • Kotenko, Sergei V
  • Fitzgerald-Bocarsly, Patricia
Type
Published Article
Journal
The Journal of Immunology
Publisher
The American Association of Immunologists
Publication Date
Sep 15, 2012
Volume
189
Issue
6
Pages
2735–2745
Identifiers
DOI: 10.4049/jimmunol.1102038
PMID: 22891284
Source
Medline
License
Unknown

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-α 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-λ receptor mRNA, as well as cell-surface IFN-λ receptor. We have developed intracellular flow cytometry assays using Abs to IFN-λ1/3 or -λ2 to assess the expression of IFN-λ proteins by pDC. We observed that a subset of human pDC expresses only intracellular IFN-α, whereas another subset produces both IFN-α and IFN-λ after stimulation with virus or the TLR9 agonist, CpG A; the cells that coexpressed IFN-α and IFN-λ were the cells with the highest levels of IFN-α expression. Ab cross-linking of CD4 or CD303 molecules on pDC inhibited both HSV-induced IFN-λ and IFN-α production. Like the production of IFN-α, the HSV-induced IFN-λ production in pDC was mediated through TLR9 and independent of virus replication. Exogenous IFN-λ treatment of pDC resulted in increased virus-induced expression of both IFN-α and IFN-λ. In addition, both exogenous IFN-λ and -α inhibited dexamethasone-induced apoptosis of pDC. We conclude that pDC are major producers of IFN-λ1 and -λ2 in response to viral stimulation and also express functional receptors for this cytokine. Thus, IFN-λ can serve as an autocrine signal to strengthen the antiviral response of pDC by increasing IFN-α and IFN-λ production, resulting in prolonged pDC survival.

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