Murine CD8α+ DCs and human BDCA3+ DCs produce large amounts of IFN-λ in response to poly IC and DNA viruses (154.6)

<jats:title>Abstract</jats:title> <jats:p>Dendritic cells (DCs) can be segregated into various subsets based on phenotypic and functional differences. Whereas plasmacytoid DCs are known for their type I interferon (IFN) producing capacity, conventional (c) DCs are better known for their roles in T cell homeostasis and priming. Among cDCs the CD8α+ subset is especially efficient in producing IL-12p70 and the induction of immunity against various pathogens and cancer. Here, we reveal a new hallmark function of murine CD8α+ cDCs and their human BDCA3+ counterparts, namely the production of large amounts of IFN-lambda (IFN-λ, also termed IL-28/29) upon stimulation with poly IC. IFN-lambdas are potent immunomodulatory and antiviral cytokines. We demonstrate that the production of IFN-λ upon poly IC injection in vivo depends on hematopoietic cells and the presence of toll-like receptor (TLR)3, interferon regulatory factor (IRF)3, IRF7, IFN-IR, Fms-related tyrosine kinase 3 ligand (FL) and IRF8 but not on myeloid differentiation factor 88 (MyD88), Rig like helicases or lymphocytes. Furthermore, we show that both CD8α+ cDCs and plasmacytoid DCs produce large amounts of IFN-λ in response to HSV-1 or parapoxvirus. Thus, IFN-λ production in response to poly IC is a novel hallmark function of mouse CD8α+ cDCs and their human equivalents.</jats:p>