title: Vaccine activation of the nutrient sensor GCN2 in dendritic cells enhances antigen presentation.
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.
authors: Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
authors: Rajesh
authors: R
authors: Ravindran
authors: 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.
authors: Nooruddin
authors: N
authors: Khan
authors: 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.
authors: Helder I
authors: HI
authors: Nakaya
authors: Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
authors: Shuzhao
authors: S
authors: Li
authors: Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
authors: Jens
authors: J
authors: Loebbermann
authors: Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
authors: Mohan S
authors: MS
authors: Maddur
authors: College of Pharmacy, Korea University, 339-700 Korea.
authors: Youngja
authors: Y
authors: Park
authors: Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA 30322, USA.
authors: Dean P
authors: DP
authors: Jones
authors: Institut National de la Santéet de la Recherche Médicale U1013, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris 75743 Paris Cedex 15, France.
authors: Pascal
authors: P
authors: Chappert
authors: Institut National de la Santéet de la Recherche Médicale U1013, Paris, France.|Université Paris Descartes, Sorbonne Paris Cité, Paris 75743 Paris Cedex 15, France.
authors: Jean
authors: J
authors: Davoust
authors: Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA 30329, USA.
authors: David S
authors: DS
authors: Weiss
authors: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors: Herbert W
authors: HW
authors: Virgin
authors: University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, UK.
authors: David
authors: D
authors: Ron
authors: 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.
authors: Bali
authors: B
authors: Pulendran
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D000071187:Autophagy-Related Protein 5; D000071193:Autophagy-Related Protein 7; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D006224:Cricetinae; D003713:Dendritic Cells / Q000201:enzymology / Q000276:immunology*; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis* / Q000235:genetics; D022341:Yellow Fever Vaccine / Q000276:immunology*
chemical_list: C495773:Atg5 protein, mouse; C502661:Atg7 protein, mouse; D000071187:Autophagy-Related Protein 5; D008869:Microtubule-Associated Proteins; D022341:Yellow Fever Vaccine; C529271:EIF2AK4 protein, human; D017346:Protein Serine-Threonine Kinases; D000071193:Autophagy-Related Protein 7