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

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.Electronic supplementary materialThe online version of this article (10.1186/s12865-018-0247-y) contains supplementary material, which is available to authorized users.

Transcriptomic Analysis of Ovine Hepatic Lymph Node Following Fasciola hepatica Infection – Inhibition of NK Cell and IgE-Mediated Signaling

“…NK cells also participate in the adaptive immune response by interacting with DC to drive adaptive responses, and prime T h 1 cells via IFN-g and TNF production (72,73). We show here that the crosstalk between DC and NK pathways is inhibited, indicating that an array of both innate and adaptive immunological processes are affected by the immunomodulatory actions of F. hepatica.…”

Dynamics of NK, CD8 and Tfh cell mediated the production of cytokines and antiviral antibodies in Chinese patients with moderate COVID‐19

“…Hence, effective therapy can be considered to be accompanied by the enhancement of both innate and acquired immune responses 23 . NK cells usually inhibit proliferation of viruses by stimulating the development of dendritic cells and CD8 + T cells via the secretion of IFN‐γ 24 . Compared with the control patients, patients with moderate COVID‐19 had a higher number of NK cells, thereby suggesting that the activity of the innate immunity against SARS‐CoV‐2 might be stronger than other pathogens.…”

Anti-cancer Therapies Employing IL-2 Cytokine Tumor Targeting: Contribution of Innate, Adaptive and Immunosuppressive Cells in the Anti-tumor Efficacy

“…It is not clear whether this effect is dependent only on IL-2-mediated activation of NK cells, or other cytolytic effector cells, such as NK-like T and/or γδ T cells not expressing CD8. In addition, both poly I:C and IFN-γ can be potent stimulators of antigen presenting cells (APC) as monocytes and monocyte-derived dendritic cells (mDC) (20, 78, 79). More importantly, APC can produce IL-12 (79), a strong inducer of NK cell cytotoxicity, and it is still to be defined whether poly I:C and IFN-γ can exert both direct and indirect effect on NK cell activation.…”

“…In addition, both poly I:C and IFN-γ can be potent stimulators of antigen presenting cells (APC) as monocytes and monocyte-derived dendritic cells (mDC) (20, 78, 79). More importantly, APC can produce IL-12 (79), a strong inducer of NK cell cytotoxicity, and it is still to be defined whether poly I:C and IFN-γ can exert both direct and indirect effect on NK cell activation. We can speculate that the crosstalk between NK and DC, further reinforced by the triggering with poly I:C and IFN-γ of both NK and DC, could generate a positive loop to produce high IL-12 and amplify NK cell response (80, 81); this could eventually generate a Th1 microenvironment favoring anti-tumor adaptive immune response (Figure 1A).…”