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.

Evolution, immunity and the emergence of brain superautoantigens

“…Stress-induced alterations of the immune response is now extensively documented and is known to rely on two main pathways: the hypothalamus-pituitary-adrenal axis and the autonomic nervous system (ASN) pathway 202, 203 . Recently, the brain reward system was also shown to deeply impact immune responses via signaling through the ASN 204 . CNS-derived superautoantigens and their instructing roles on immune repertoires could thus provide another mechanism of brain-induced immunomodulation.…”

Molecular and Functional Neuroscience in Immunity

“…These effects are mediated through central mAChRs and the vagus nerve. A recent study highlighted the involvement of dopaminergic signaling in the regulation of peripheral immune function (145). Selective chemogenetic stimulation of dopaminergic receptors in the ventral tegmental area results in augmented macrophage and dendritic cell phagocytic activity, macrophage and monocyte bactericidal activation, and suppressed bacterial accumulation in the liver (145).…”

“…A recent study highlighted the involvement of dopaminergic signaling in the regulation of peripheral immune function (145). Selective chemogenetic stimulation of dopaminergic receptors in the ventral tegmental area results in augmented macrophage and dendritic cell phagocytic activity, macrophage and monocyte bactericidal activation, and suppressed bacterial accumulation in the liver (145). These effects are abrogated in animals with disrupted sympathetic catecholaminergic neurons, pointing to their mediating role in enhancing antibacterial immune activation (145).…”

The psychology of neurofeedback: Clinical intervention even if applied placebo.

“…In a blinded study, researchers found that 28 of 34 epileptic dogs responded to placebo treatment (Munana, Zhang, & Patterson, 2010). Research further documents a range of placebo phenomena in non-human animals for a spectrum of objective measures, including antibody production (Ader, Kelly, Moynihan, Grota, & Cohen, 1993;Jaeger, Larsen, & Moe, 2006;McMillan, 1999) and bacterial immunity (Ben-Shaanan et al, 2016).…”