Polyinosinic:polycytidylic acid (poly IC), a double-stranded RNA, is an effective adjuvant in vivo. IFN-λs (also termed IL-28/29) are potent immunomodulatory and antiviral cytokines. We demonstrate that poly IC injection in vivo induces large amounts of IFN-λ, which depended on hematopoietic cells and the presence of TLR3 (Toll-like receptor 3), IRF3 (IFN regulatory factor 3), IRF7, IFN-I receptor, Fms-related tyrosine kinase 3 ligand (FL), and IRF8 but not on MyD88 (myeloid differentiation factor 88), Rig-like helicases, or lymphocytes. Upon poly IC injection in vivo, the IFN-λ production by splenocytes segregated with cells phenotypically resembling CD8α + conventional dendritic cells (DCs cDCs). In vitro experiments revealed that CD8α + cDCs were the major producers of IFN-λ in response to poly IC, whereas both CD8α + cDCs and plasmacytoid DCs produced large amounts of IFN-λ in response to HSV-1 or parapoxvirus. The nature of the stimulus and the cytokine milieu determined whether CD8α + cDCs produced IFN-λ or IL-12p70. Human DCs expressing BDCA3 (CD141), which is considered to be the human counterpart of murine CD8α + DCs, also produced large amounts of IFN-λ upon poly IC stimulation. Thus, IFN-λ production in response to poly IC is a novel function of mouse CD8α + cDCs and their human equivalents. Footnotes Abbreviations used: cDC conventional DC DN double negative dsRNA double-stranded RNA DT diphtheria toxin DTR DT receptor FL Fms-related tyrosine kinase 3 ligand IFN-IR IFN-I receptor IRF IFN regulatory factor ODN oligonucleotide pDC plasmacytoid DC poly IC polyinosinic:polycytidylic acid PRR pattern recognition receptor RLH Rig-like helicase TLR Toll-like receptor Submitted: 21 December 2009 Accepted: 30 September 2010 This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms ). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/ ).
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Mouse CD8α+ DCs and human BDCA3+ DCs are major producers of IFN-λ in response to poly IC
Lauterbach, Henning; Bathke, Barbara; Gilles, Stefanie; Traidl-Hoffmann, Claudia; Luber, Christian A.; Fejer, György; Freudenberg, Marina A.; Davey, Gayle M.; Vremec, David; Kallies, Axel; Wu, Li; Shortman, Ken; Chaplin, Paul; Suter, Mark; O’Keeffe, Meredith; Hochrein, Hubertus
Follow The Journal of Experimental Medicine
, Volume 207 (12): 2703
Rockefeller University Press – Nov 22, 2010
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