Vaccine Activation of the Nutrient Sensor GCN2 in Dendritic Cells Enhances Antigen Presentation

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NIAID-funded Study Reveals Enzyme’s Novel Role in Immune Response to Vaccines
Researchers at Emory University have shown that an enzyme involved in cellular responses to nutrient shortages also plays a role in vaccine-induced immune responses. The yellow fever vaccine and a certain type of influenza vaccine activate the enzyme, called GCN2, stimulating pathways that lead to specific immune responses. Finding ways to activate this process may lead to the development of better vaccines.
The results of this NIAID-funded study appear in the December 5 issue of Science Express. The researchers’ findings highlight the complexity of vaccine-induced immune responses and suggest a potential target to enhance vaccine-induced immunity.
For more information about the study, read the abstract in Science Express.

Published Online December 5 2013
< Science Express Index
Science DOI: 10.1126/science.1246829

• Report

Vaccine Activation of the Nutrient Sensor GCN2 in Dendritic Cells Enhances Antigen Presentation

1. Rajesh Ravindran¹,*,
2. Nooruddin Khan²,*,
3. Helder I. Nakaya¹,³,
4. Shuzhao Li¹,
5. Jens Loebbermann¹,
6. Mohan S. Maddur¹,
7. Youngja Park⁴,
8. Dean P. Jones⁵,
9. Pascal Chappert⁶,⁷,
10. Jean Davoust⁶,⁷,
11. David S. Weiss⁸,
12. Herbert W. Virgin⁹,
13. David Ron¹⁰,
14. Bali Pulendran¹,³,†

1. ¹Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30329, USA.
2. ²Department of Biotechnology, School of Life Sciences, University of Hyderabad, Hyderabad, India.
3. ³Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA, USA.
4. ⁴College of Pharmacy, Korea University, 339-700 Korea.
5. ⁵Department of Medicine, Division of Pulmonary, Allergy and Critical Care, Emory University, Atlanta, GA, USA.
6. ⁶Institut National de la Santé et de la Recherche M′edicale U1013, Paris, France.
7. ⁷Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
8. ⁸Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA, USA .
9. ⁹Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
10. ¹⁰University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Cambridge CB2 0QQ, England.

1. ↵†Corresponding author. E-mail: bpulend{at}emory.edu

1. ↵* These authors contributed equally to this work.

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 over 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 GCN2 in the blood strongly correlates with the magnitude of the later CD8⁺ T cell response. Here 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.

• Received for publication 4 October 2013.
• Accepted for publication 20 November 2013.