Toll-like receptor ligands synergize through distinct dendritic cell pathways to induce T cell responses: implications for vaccines.

Abstract

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.

• Authors: Qing Zhu, Colt Egelston, Aravindhan Vivekanandhan, Satoshi Uematsu, Shizuo Akira, Dennis M Klinman, Igor M Belyakov, Jay A Berzofsky
• Journal: Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 105 Issue 42 Pg. 16260-5 (Oct 21 2008) ISSN: 1091-6490 [Electronic] United States
• PMID: 18845682 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Ligands
• Myeloid Differentiation Factor 88
• Toll-Like Receptors
• Vaccines

Topics

• Animals
• Cells, Cultured
• Dendritic Cells (immunology, metabolism)
• Female
• Ligands
• Lymphocyte Activation (immunology)
• Mice
• Mice, Knockout
• Myeloid Differentiation Factor 88 (deficiency, genetics, metabolism)
• Signal Transduction (immunology)
• T-Lymphocytes (immunology, metabolism)
• Toll-Like Receptors (metabolism)
• Vaccines (immunology)