Natural killer (NK) cells constitute a major component of the innate immune system and have key roles in early immune responses to pathogens. Although NK cells can be directly activated by pathogens, other sensor cells which recognize pathogen-associated pattern molecules are required for the full activation of NK cells. The NK-activating capacity is observed in myeloid dendritic cells (mDCs), plasmacytoid DCs, macrophages and monocytes. The tropism of the pathogen and the route of invasion influence which sensor cells participate in the NK activation. Influenza virus, measles virus and respiratory syncytial virus can infect human mDCs and induce the ligands of the NK activating receptor NKG2D. Up-regulated NKG2D ligands on mDCs contribute to the mDC-mediated NK activation. By contrast, HCV does not replicate in mDCs and is not an immunostimulatory agent against mDCs. In this case, mDCs are stimulated after detecting dsRNA in the HCV-infected apoptotic hepatocytes via TLR3 and elicit NK activation though a direct cell/cell contact. The TLR3 signal seems to lead the up-regulation of key molecules on the surface membrane of mDCs to enhance NK activity by direct linkage.
Keywords: Dendritic cell, NK cell, RNA virus, hepatitis C virus, dsRNA, Toll like receptor 3
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