Interferons, specifically Type I interferons, activate natural killer (NK) cells through direct mechanisms and also indirectly, often involving the cytokine IL-15.
Mechanisms of NK Cell Activation by Interferons
Type I interferons play a crucial role in the immune response, particularly against viral infections. Their interaction with NK cells is a key component of this defense. Activation can occur via distinct pathways:
Direct Activation
Type I interferons can directly stimulate NK cells. This means the interferons interact straight with receptors on the surface of NK cells, triggering signaling pathways within the NK cell that lead to increased activity and function.
Indirect Activation via IL-15 Presentation
Beyond direct stimulation, Type I interferons also promote NK cell activation indirectly. A significant way this happens is through the presentation of Interleukin-15 (IL-15). This presentation can occur via two mechanisms:
- Cis-presentation: IL-15 is presented on the surface of the same cell that produces it, typically in conjunction with a receptor component.
- Trans-presentation: A different cell presents IL-15 to the NK cell.
Both cis and trans presentation of IL-15, facilitated by Type I interferons, enhance NK cell responsiveness and activation.
Signal Transduction and IFN-γ Production
Early exposure of NK cells to Type I interferons during an antiviral immune response triggers specific internal signaling events. This involves the preferential activation (phosphorylation) of a signaling protein called STAT4 over another protein called STAT1. This specific pattern of STAT activation is important because it leads to the production of Interferon-gamma (IFN-γ) by the NK cells, a potent cytokine that further enhances the immune response.
In summary, Type I IFNs bolster the activity of NK cells through multiple avenues, ensuring a robust early response against pathogens like viruses.
