Pathogen recognition by NK cells amplifies the pro-inflammatory cytokine production of monocyte-derived DC via IFN-γ

Background: Besides their prominent role in the elimination of infected or malignantly transformed cells, natural killer (NK) cells serve as modulators of adaptive immune responses. Enhancing bidirectional crosstalk between NK cells and dendritic cells (DC) is considered a promising tool to potentiate cancer vaccines. We investigated to what extent direct sensing of viral and bacterial motifs by NK cells contributes to the response of inflammatory DC against the same pathogenic stimulus. Results: We demonstrated that sensing of bacterial and viral PAMPs by NK cells contributes to DC cytokine production via NK cell-derived soluble factors. This enhancement of DC cytokine production was dependent on the pattern recognition receptor (PRR) agonist but also on the cytokine environment in which NK cells recognized the pathogen, indicating the importance of accessory cell activation for this mechanism. We showed in blocking experiments that NK cell-mediated amplification of DC cytokine secretion is dependent on NK cell-derived IFN-gamma irrespective of the PRR that is sensed by the NK cell. Conclusions: These findings illustrate the importance of bidirectional interaction between different PRR-expressing immune cells, which can have implications on the selection of adjuvants for vaccination strategies.