title: Activation of the reward system boosts innate and adaptive immunity.
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.
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Center of Science and Engineering of Neuronal Systems, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Tamar L
authors.initials: TL
authors.lastname: Ben-Shaanan
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Center of Science and Engineering of Neuronal Systems, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Hilla
authors.initials: H
authors.lastname: Azulay-Debby
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Tania
authors.initials: T
authors.lastname: Dubovik
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Elina
authors.initials: E
authors.lastname: Starosvetsky
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Center of Science and Engineering of Neuronal Systems, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Ben
authors.initials: B
authors.lastname: Korin
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Center of Science and Engineering of Neuronal Systems, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Maya
authors.initials: M
authors.lastname: Schiller
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Center of Science and Engineering of Neuronal Systems, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Nathaniel L
authors.initials: NL
authors.lastname: Green
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Admon
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Pediatric Pulmonary Unit, Rambam Health Care Campus, Haifa, Israel.
authors.forename: Fahed
authors.initials: F
authors.lastname: Hakim
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Faculty of Biology, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Shai S
authors.initials: SS
authors.lastname: Shen-Orr
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.|Center of Science and Engineering of Neuronal Systems, Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
authors.forename: Asya
authors.initials: A
authors.lastname: Rolls
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001419:Bacteria; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology; D005434:Flow Cytometry; D006968:Hypersensitivity, Delayed / Q000276:immunology*; D007113:Immunity, Innate / Q000276:immunology*; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D010587:Phagocytosis / Q000276:immunology; D015990:Placebo Effect; D012201:Reward; D013563:Sympathectomy, Chemical; D013564:Sympathetic Nervous System / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D017557:Ventral Tegmental Area / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines