Zhu Qing, Egelston Colt, Vivekanandhan Aravindhan, Uematsu Satoshi, Akira Shizuo, Klinman Dennis M, Belyakov Igor M, Berzofsky Jay A
Vaccine Branch, Center for Cancer Research, and Laboratory of Experimental Immunology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Proc Natl Acad Sci U S A. 2008 Oct 21;105(42):16260-5. doi: 10.1073/pnas.0805325105. Epub 2008 Oct 9.
Toll-like receptors (TLRs) may need to cooperate with each other to be effective in detecting imminent infection and trigger immune responses. Understanding is still limited about the intracellular mechanism of this cooperation. We found that when certain TLRs are involved, dendritic cells (DCs) establish unidirectional intracellular cross-talk, in which the MyD88-independent TRIF-dependent pathway amplifies the MyD88-dependent DC function through a JNK-dependent mechanism. The amplified MyD88-dependent DC function determines the induction of the T cell response to a given vaccine in vivo. Therefore, our study revealed an underlying TLR mechanism governing the functional, nonrandom interplay among TLRs for recognition of combinatorial ligands that may be dangerous to the host, providing important guidance for design of novel synergistic molecular vaccine adjuvants.
Toll样受体（TLRs）可能需要相互协作，才能有效地检测即将发生的感染并触发免疫反应。目前对于这种协作的细胞内机制的了解仍然有限。我们发现，当某些TLRs参与其中时，树突状细胞（DCs）会建立单向的细胞内串扰，其中不依赖MyD88的TRIF依赖途径通过JNK依赖机制放大依赖MyD88的DC功能。放大的依赖MyD88的DC功能决定了体内T细胞对给定疫苗反应的诱导。因此，我们的研究揭示了一种潜在的TLR机制，该机制控制着TLRs之间功能性、非随机的相互作用，以识别可能对宿主有害的组合配体，为新型协同分子疫苗佐剂的设计提供了重要指导。
