With increasing interest in alternative options to interferon-alpha-based treatments, IFN-λ has shown therapeutic promise in a variety of diseases. Although the antiviral activity of IFN-λ has been extensively studied, there is limited knowledge regarding the immunological functions of IFN-λ and how these differ from those of other classes of IFNs. In this study, we investigated the effects of IFN-λ on primary human NK cells, both in a direct and indirect capacity. We demonstrate that in contrast to interferon-alpha, IFN-λ is unable to directly stimulate NK cells, due to the absence of IFN-λ receptor chain 1 (IFN-λR1) on NK cells. However, IFN-λ, in combination with TLR4 challenge, is able to induce the production of select members of the IL-12 family of cytokines in monocyte-derived macrophages. We further show that through macrophage-mediated IL-12 production, IFN-λ is able to indirectly affect NK cells and ultimately induce IFN-γ production.

Additional Metadata
Keywords Hepatitis C, IFN-γ, IL-29, Innate immunity, Macrophages, NK cells
Persistent URL dx.doi.org/10.1002/eji.201444903, hdl.handle.net/1765/89515
Journal European Journal of Immunology
Citation
de Groen, R.A, Boltjes, A, Hou, J, Liu, B.-S, McPhee, F, Friborg, J, … Boonstra, P.A. (2015). IFN-λ-mediated IL-12 production in macrophages induces IFN-γ production in human NK cells. European Journal of Immunology, 45(1), 250–259. doi:10.1002/eji.201444903