Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity

Speaker: 陳美君                            Time: PM 2:00~3:00; 05/24/2006

Commentator: 蕭璦莉 老師                  Place: Room 601

Abstract:

Yellow fever (YF) is once again emerging as an important infectious disease in Africa, South America, and Central America, which is transmitted by mosquitoes and can cause symptoms such as high fevers accompanied by prostration, headache, and malaise. The yellow fever vaccine YF-17D is a live attenuated vaccine that has been used for almost 70 years on more than 400 million people with a remarkable record of safety and efficacy (1). Despite of its efficacy, only recently have YF-specific human CD8⁺ T cell responses been identified, but the immunological mechanisms by which YF-17D acts remain unclear. For innate immunity, dendritic cells (DCs) play a critical role in sensing pathogen invasion and initiating the adaptive immune responses through Toll-like receptors (TLRs). Some studies suggest that the quality of the adaptive immune response is partly determined by the particular TLR triggered, as well as by the particular subset of DC activated (2). In this paper, the authors showed that YF-17D could activate multiple subsets of human and mouse dendritic cells and induce the proinflammatory cytokine production, such as IL-6, TNF-a, and MCP-1. Furthermore, by use of DCs from wild-type mice and TLR2, 4, 7, and 9 knockout mice to determine precisely which TLRs were activated by YF-17D, they found that TLR2, 7 and 9 but not TLR4 played a role in response to YF-17D. NF-kB activation in HEK293 cells transfected with human TLR8 could be observed in response to YF-17D. Moreover, YF-17D could induce both Th1 and Th2 cytokines, IFN-g and IL-4, IL-5, IL-13, and IL-10, reflecting that a mixed Th1/Th2 responses through distinct TLRs were stimulated. In conclusion, these data suggest that the YF-17D elicites the synergistic immune responses, and thus provide the potential of vaccination strategies that use combination of different TLR ligands to stimulate polyvalent immune responses (3).

References:

1.     Theiler, M. and H. H. Smith. 2000. The use of yellow fever virus modified by in vitro cultivation for human immunization. Rev. Med. Virol. 10: 3-16.

2.     Iwasaki, A. and R. Medzhitov. 2004. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 5: 987-995.

3.     Querec, T. et al. 2006. Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. J. Exp. Med. 203: 413-424.