Activation of the reward system boosts innate and adaptive immunity

Tamar L. Ben-Shaanan, Hilla Azulay-Debby, Tania Dubovik, Elina Starosvetsky, Ben Korin, Maya Schiller, Nathaniel L. Green, Yasmin Admon, Fahed Hakim, Shai S. Shen-Orr, Asya Rolls

Research output: Contribution to journalArticlepeer-review

155 Scopus citations

Abstract

Positive expectations contribute to the clinical benefits of the placebo effect. Such positive expectations are mediated by the brain's reward system; however, it remains unknown whether and how reward system activation affects the body's physiology and, specifically, immunity. Here we show that activation of the ventral tegmental area (VTA), a key component of the reward system, strengthens immunological host defense. We used 'designer receptors exclusively activated by designer drugs' (DREADDs) to directly activate dopaminergic neurons in the mouse VTA and characterized the subsequent immune response after exposure to bacteria (Escherichia coli), using time-of-flight mass cytometry (CyTOF) and functional assays. We found an increase in innate and adaptive immune responses that were manifested by enhanced antibacterial activity of monocytes and macrophages, reduced in vivo bacterial load and a heightened T cell response in the mouse model of delayed-type hypersensitivity. By chemically ablating the sympathetic nervous system (SNS), we showed that the reward system's effects on immunity are, at least partly, mediated by the SNS. Thus, our findings establish a causal relationship between the activity of the VTA and the immune response to bacterial infection.

Original languageEnglish
Pages (from-to)940-944
Number of pages5
JournalNature Medicine
Volume22
Issue number8
DOIs
StatePublished - 1 Aug 2016
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2016 Nature America, Inc. All rights reserved.

Funding

We would like to thank A. Ziv-Kenet for his help with CyTOF data analysis, A.D. Eban-Rothchild, C. Tourino, D. Melamed, N. Karin, G. Wildbaum, R. Hershberg and M. Rahat for helpful discussions, A. Mor, F. Zaknoon, J. Jammal, S. Yaron and S. Katz for their help with bacterial experiments, Y. Posen, G. Ginzburg and E. Reisin-Tzur for editing the paper, H. Amitay for her help with the behavioral analysis, and O. Goldberger and the Biomedical core facility at the Technion Faculty of Medicine for technical support. This research was supported by the FP-7-CIG grant 618654 (A.R.), the Israel Science Foundation (ISF) grants 1862/15 (A.R.) and 1365/12 (S.S.S.-O.), the Technion V.P.R. Fund-Malat Family (A.R.), the Adelis Foundation (A.R.) and the Rappaport Institute of Biomedical Research (S.S.S.-O.).

FundersFunder number
Rappaport Institute of Biomedical Research
Technion V.P.R. Fund-Malat Family
Achelis Foundation
Israel Science Foundation1862/15, 1365/12

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