Viral infection and toll-like receptor agonists induce a differential expression of type I and λ interferons in humans plasmacytoid and monocyte-derived dendritic cells

Abstract

In humans, the type I interferon (IFN) family consists of 13 IFN-α subtypes, IFN-β and IFN-ω; the newly discovered IFN-like family consists of IFN-λ1, -λ2 and -λ3. We have investigated the expression of type I and λ IFN genes following virus infections or Toll-like receptor (TLR) triggering in monocyte-derived DC (MDDC) and plasmacytoid DC (pDC). We found that all IFN-α, -β, -ω and -λ subtypes are expressed in influenza-virus-infected MDDC or pDC. Conversely, differential type I IFN gene transcription was induced in MDDC and pDC stimulated by specific TLR agonists. TLR-9 stimulation by CpG DNA induced the expression of all IFN-α, -β, -ω and -λ subtypes in pDC, whereas TLR-4 stimulation by LPS, or TLR-3 stimulation by poly I:C, induced only IFN-β and IFN-λ gene expression in MDDC. The expression pattern of IFN regulatory factor (IRF)-5 and IRF-7 in MDDC and pDC was also determined. IRF-5 was constitutively expressed in the two DC subsets whereas IRF-7 was constitutive in pDC but its expression was induced along MDDC maturation. Overall, our data indicate that the coordinated expression of IFN-λ with IFN-β would be of crucial importance for the maturation of DC. © 2004 Wiley-VCH Verlag GmbH & Co.