Toll-like receptors (TLRs) and NK cell receptors are the most important receptor superfamilies in innate immunity. TLRs act as the sensor of external pathogens, while NK cells detect alterations in endogenous protein expression on target cells through activating and inhibitory receptors. Accumulating data has demonstrated that TLRs and NK cell receptors can coordinate and regulate each other during immune responses, which contributes to the initiation of innate response and the priming of adaptive responses. TLRs can activate NK cell function directly or with the help of accessory cells in a cytokine or cell-to-cell contact dependent manner. More understanding of the recognition of innate receptors and interactions between them may provide important insights into the design of effective strategies to combat tumor and microbial infections. In this review, we summarize how TLRs and NK cells discriminate the self or non-self components respectively. And importantly, we pay more attention to the role of TLR sig-naling in induction of NK cell activation, responses and the crosstalk between them.
Toll-like receptors(TLRs)are a family of highly conserved germline-encoded pattern-recognition receptors that are essential for host immune responses.TLR ligands represent a promising class of immunotherapeutics or vaccine adjuvants with the potential to generate an effective antitumor immune response.The TLR7/8 agonists have aroused interest because they not only activate antigen-presenting cells but also promote activation of T and natural killer(NK)cells.However,the exact mechanism by which stimulation of these TLRs promotes immune responses remains unclear,and different TLR7/8 agonists have been found to induce different responses.In this study,we demonstrate that both gardiquimod and imiquimod promote the proliferation of murine splenocytes,stimulate the activation of splenic T,NK and natural killer T(NKT)cells,increase the cytolytic activity of splenocytes against B16 and MCA-38 tumor cell lines,and enhance the expression of costimulatory molecules and IL-12 by macrophages and bone marrow-derived dendritic cells(DCs).In a murine model,both agonists improved the antitumor effects of tumor lysate-loaded DCs,resulting in delayed growth of subcutaneous B16 melanoma tumors and suppression of pulmonary metastasis.Further,we found that gardiquimod demonstrated more potent antitumor activity than imiquimod.These results suggest that TLR7/8 agonists may serve as potent innate and adaptive immune response modifiers in tumor therapy.More importantly,they can be used as vaccine adjuvants to potentiate the efficiency of DC-based tumor immunotherapy.
