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pubmed:abstractText |
Polyinosinic:polycytidylic acid (poly IC), a double-stranded RNA, is an effective adjuvant in vivo. IFN-?s (also termed IL-28/29) are potent immunomodulatory and antiviral cytokines. We demonstrate that poly IC injection in vivo induces large amounts of IFN-?, 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-? production by splenocytes segregated with cells phenotypically resembling CD8?(+) conventional dendritic cells (DCs [cDCs]). In vitro experiments revealed that CD8?(+) cDCs were the major producers of IFN-? in response to poly IC, whereas both CD8?(+) cDCs and plasmacytoid DCs produced large amounts of IFN-? in response to HSV-1 or parapoxvirus. The nature of the stimulus and the cytokine milieu determined whether CD8?(+) cDCs produced IFN-? or IL-12p70. Human DCs expressing BDCA3 (CD141), which is considered to be the human counterpart of murine CD8?(+) DCs, also produced large amounts of IFN-? upon poly IC stimulation. Thus, IFN-? production in response to poly IC is a novel function of mouse CD8?(+) cDCs and their human equivalents.
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