Abstract
BackgroundBesides 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.ResultsWe 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-γ irrespective of the PRR that is sensed by the NK cell.ConclusionsThese 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.
Highlights
Besides their prominent role in the elimination of infected or malignantly transformed cells, natural killer (NK) cells serve as modulators of adaptive immune responses
We aimed to investigate in more detail whether the direct recognition of specific viral and bacterial Pathogen-associated molecular pattern (PAMP) by NK cells contributes to an increased activation of mo-dendritic cells (DC) exposed to the same trigger during the initial phase of DC maturation
Viral PAMP-recognition by NK cells induces their activation in the presence of IL-2 To evaluate and confirm whether NK cells recognize and get activated after engagement of different viral PAMPs, we incubated NK cells with different viral Toll-like receptors (TLR) ligands: poly(I:C) (TLR3), gardiquimod (TLR7), CL075 and R848, ssRNA40 and sspolyU
Summary
Besides their prominent role in the elimination of infected or malignantly transformed cells, natural killer (NK) cells serve as modulators of adaptive immune responses. Natural killer (NK) cells are important players of the innate immune system and are well described for their role in controlling viral infections and limiting tumour outgrowth by recognizing and eliminating altered selfcells [1,2,3]. The presence of viral or bacterial pathogens is sensed by pattern recognition receptors (PRR). These receptors recognize conserved microbial structures, the so-called pathogen-associated molecular patterns (PAMPs). PAMP-matured DC have the capacity to activate NK cells by soluble as well as contactdependent factors
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