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PMID: 24310610 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation.

Science (New York, N.Y.) ·Vol. 343 ·No. 6168 ·2014-01-17 ·Pages 313-317

Ravindran R, Khan N, Nakaya HI, Li S, Loebbermann J, Maddur MS, Park Y, Jones DP, Chappert P, Davoust J, Weiss DS, Virgin HW, Ron D, Pulendran B

Abstract

The yellow fever vaccine YF-17D is one of the most successful vaccines ever developed in humans. Despite its efficacy and widespread use in more than 600 million people, the mechanisms by which it stimulates protective immunity remain poorly understood. Recent studies using systems biology approaches in humans have revealed that YF-17D-induced early expression of general control nonderepressible 2 kinase (GCN2) in the blood strongly correlates with the magnitude of the later CD8(+) T cell response. We demonstrate a key role for virus-induced GCN2 activation in programming dendritic cells to initiate autophagy and enhanced antigen presentation to both CD4(+) and CD8(+) T cells. These results reveal an unappreciated link between virus-induced integrated stress response in dendritic cells and the adaptive immune response.

MeSH Terms
Animals Antigen Presentation Autophagy-Related Protein 5 Autophagy-Related Protein 7 CD4-Positive T-Lymphocytes/immunology CD8-Positive T-Lymphocytes/immunology Cell Line Cricetinae Dendritic Cells/enzymology,immunology Enzyme Activation Humans Mice Mice, Inbred C57BL Mice, Mutant Strains Microtubule-Associated Proteins/genetics Protein Serine-Threonine Kinases/biosynthesis,genetics Yellow Fever Vaccine/immunology
Chemicals
Atg5 protein, mouse Atg7 protein, mouse Autophagy-Related Protein 5 Microtubule-Associated Proteins Yellow Fever Vaccine EIF2AK4 protein, human Protein Serine-Threonine Kinases Autophagy-Related Protein 7
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Ravindran Rajesh
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
Khan Nooruddin
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA. | Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad 500046, India.
Nakaya Helder I
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA. | Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
Li Shuzhao
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
Loebbermann Jens
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
Maddur Mohan S
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
Park Youngja
College of Pharmacy, Korea University, 339-700 Korea.
Jones Dean P
Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA 30322, USA.
Chappert Pascal
Institut National de la Santéet de la Recherche Médicale U1013, Paris, France. | Université Paris Descartes, Sorbonne Paris Cité, Paris 75743 Paris Cedex 15, France.
Davoust Jean
Institut National de la Santéet de la Recherche Médicale U1013, Paris, France. | Université Paris Descartes, Sorbonne Paris Cité, Paris 75743 Paris Cedex 15, France.
Weiss David S
Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA 30329, USA.
Virgin Herbert W
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Ron David
University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
Pulendran Bali
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA. | Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA.
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Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1246829
Published
2014-01-17
Epub
2013-00-05
Pages
313-317
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC4048998
Subset
IM
Grants
NIAID NIH HHS · R37 AI048638 · United States
NIAID NIH HHS · R38 AI140299 · United States
NIAID NIH HHS · U19 AI090023 · United States
NIH HHS · P51 OD011132 · United States
NIAID NIH HHS · R56 AI048638 · United States
NIDDK NIH HHS · R37 DK057665 · United States
Wellcome Trust · 084812 · United Kingdom
NIAID NIH HHS · U54 AI057160 · United States
NIAID NIH HHS · N01 AI050019 · United States
Wellcome Trust · 084812/Z/08/Z · United Kingdom
NIAID NIH HHS · U54 AI057157 · United States
NIAID NIH HHS · U19 AI057266 · United States
NIAID NIH HHS · N01 AI050025 · United States
External Links
PubMed source DOI: 10.1126/science.1246829 PMC Full Text View journal details
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