Natural killer cell activation secondary to innate pattern sensing

Abstract

Recent progress in understanding the outcomes of pattern-recognition by myeloid dendritic cells (mDC) allows us to delineate the pathways driving natural killer (NK) cell activation. Mouse mDC mature in response to microbial patterns and are converted to an NK cell-activating phenotype. The MyD88 pathway, the Toll/IL-1 receptor homology domain-containing adaptor molecule (TICAM)-1 (TRIF) pathway, and the interferon (IFN)-β promoter stimulator 1 (IPS-1) pathway in mDC participate in driving NK activation, as shown by analyses in knockout mice. Studies using synthetic compounds for Toll-like receptors/RIG-I-like receptors have demonstrated that mDC-NK cell contact induces NK cell activation without the participation of cytokines in mice. In vivo bone marrow transplantation analysis revealed that the IPS-1 pathway in nonmyeloid cells and the TICAM-1 pathway in mDC are crucial for dsRNA-mediated in vivo NK activation. These results infer the presence of cytokine-dependent and cytokine-independent modes of NK activation in conjunction with innate immune activation. Here, we focus on the IFN-inducing pathways and mDC-NK contact-induced NK activation and discuss the reported various NK activation modes.