Yellow fever vaccine YF-17D activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity
Troy D. Querec,Soumaya Bennouna,Sefik S. Alkan,Yasmina Laouar,Keith B. Gorden,Richard A. Flavell,Shizuo Akira,Rafi Ahmed,Bali Pulendran +8 more
TLDR
Data is presented that suggest that YF-17D activates multiple Toll-like receptors on dendritic cells (DCs) to elicit a broad spectrum of innate and adaptive immune responses, and highlights the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses.Abstract:
The live attenuated yellow fever vaccine 17D (YF-17D) is one of the most effective vaccines available, with a 65-yr history of use in >400 million people globally. Despite this efficacy, there is presently no information about the immunological mechanisms by which YF-17D acts. Here, we present data that suggest that YF-17D activates multiple Toll-like receptors (TLRs) on dendritic cells (DCs) to elicit a broad spectrum of innate and adaptive immune responses. Specifically, YF-17D activates multiple DC subsets via TLRs 2, 7, 8, and 9 to elicit the proinflammatory cytokines interleukin (IL)-12p40, IL-6, and interferon-α. Interestingly, the resulting adaptive immune responses are characterized by a mixed T helper cell (Th)1/Th2 cytokine profile and antigen-specific CD8+ T cells. Furthermore, distinct TLRs appear to differentially control the Th1/Th2 balance; thus, whilst MyD88-deficient mice show a profound impairment of Th1 cytokines, TLR2-deficient mice show greatly enhanced Th1 and Tc1 responses to YF-17D. Together, these data enhance our understanding of the molecular mechanism of action of YF-17D, and highlight the potential of vaccination strategies that use combinations of different TLR ligands to stimulate polyvalent immune responses.read more
Citations
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Taking dendritic cells into medicine
TL;DR: Some medical implications of DC biology that account for illness and provide opportunities for prevention and therapy are presented.
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Vaccine Adjuvants: Putting Innate Immunity to Work
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Cooperation of Toll-like receptor signals in innate immune defence.
Giorgio Trinchieri,Alan Sher +1 more
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Correlates of Protection Induced by Vaccination
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Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans
Troy D. Querec,Rama Akondy,Eva K. Lee,Weiping Cao,Helder I. Nakaya,Dirk E. Teuwen,Ali A. Pirani,Kim M. Gernert,Jiusheng Deng,Bruz Marzolf,Kathleen A. Kennedy,Haiyan Wu,Soumaya Bennouna,Herold Oluoch,Joseph I. Miller,Ricardo Z. N. Vêncio,Mark J. Mulligan,Alan Aderem,Rafi Ahmed,Bali Pulendran,Bali Pulendran +20 more
TL;DR: This article used a system biology approach to identify early gene signatures that predicted immune responses in humans vaccinated with the yellow fever vaccine YF-17D, with up to 90% accuracy in an independent, blinded trial.
References
More filters
Journal ArticleDOI
Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene
Alexander Poltorak,Xiaolong He,Irina Smirnova,Mu Ya Liu,Christophe Van Huffel,Xin Du,Dale Birdwell,E. Alejos,M. Silva,Chris Galanos,Marina Freudenberg,Paola Ricciardi-Castagnoli,Betsy Layton,Bruce Beutler +13 more
TL;DR: The mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane.
Journal Article
Defective LPS signaling in C3 H/HeJ and C57 BL/10 ScCr mice: Mutations in Tlr4 Gene
Alexander Poltorak,Xiaolong He,Irina Smirnova,Mu Ya Liu,C. Van Huffel,Xin Du,Dale Birdwell,E. Alejos,M. Suva,Chris Galanos,Marina Freudenberg,Paola Ricciardi-Castagnoli,B. Layton,Bruce Beutler +13 more
Journal ArticleDOI
Recognition of double-stranded RNA and activation of NF-kappaB by Toll-like receptor 3.
TL;DR: It is shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB and the production of type I interferons (IFNs).
Journal ArticleDOI
Toll-like receptors.
TL;DR: This unit discusses mammalian Toll receptors (TLR1‐10) that have an essential role in the innate immune recognition of microorganisms and are discussed are TLR‐mediated signaling pathways and antibodies that are available to detect specific TLRs.
Journal ArticleDOI
Tolerance, danger, and the extended family.
TL;DR: The possibility that the immune system does not care about self and non-self, that its primary driving force is the need to detect and protect against danger, and that it does not do the job alone, but receives positive and negative communications from an extended network of other bodily tissues is discussed.
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