Interaction between conventional dendritic cells and natural killer cells is integral to the activation of effective antiviral immunity

Nat. Immunol. 6, 1011-1019 (2005).

Speaker:徐英展                            Time: 2005/11/16 15:10~16:00

Commentator:徐麗君 老師                   Place: Room 601

Abstract:

It is known that some interactions between dendritic cells (DCs) and NK cells¹ would up-regulate NK cells activity. Dendritic cells activate NK cells either by secreting some cytokines such as IFN-α, IL-2 and IL-12, or by direct contact on NK cells. DCs are classified into three main subsets: conventional (CD11b⁺ DCs) or CD8α⁺ DCs and plasmacytoid DCs(pDCs). In the murine cytomegalovirus (MCMV) infection model, conventional CD11b⁺ DCs are the prominent targets for MCMV² and NK are required for the early control of MCMV replication³. Therefore the authors investigate how the DCs could contribute to NK cell activation during MCMV infection. After MCMV infection, the infected CD11b⁺ cells activate the NK cell. DC-derived IL-12 and IL-18 contributes to IFN-γ production by NK cells, but NK cell cytotoxicity requires IFN-αand the interaction between the NKG2D activating receptor and NKG2D ligand on CD11b⁺ DCs. Adoptive transfer of MCMV-stimulated CD 11b⁺ DCs could inhibit MCMV replication in vivo. Although the IFN-α-produced by plasmacytoid DCs is TLR-9 dependent, IFN-α production by CD11b⁺ DCs is independently of TLR9. And CD11b⁺ DCs-induced NK cell cytotoxicity is also independently of TLR9. These results demonstrate that CD11b⁺ DCs are a critical component of the early antiviral response to MCMV infection. After infection, CD11b⁺ DCs produced IFN-α and activated NK cells by NKG2D-NKG2DL interaction. These pathways are independent of TLR9 that CD11b⁺ DCs can recognize MCMV.

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