Patient expectation and the activation of brain reward circuitry have a role in placebo-related clinical benefits, but the mechanism is unknown. Ben-Shaanan et al. show that chemogenetic activation of neurons in the ventral tegmental area followed by exposure to Escherichia coli resulted in increased bactericidal activity of monocytes and macrophages, which was lost after ablation of peripheral catecholaminergic neurons of the sympathetic nervous system. This suggests that neurons of the ventral tegmental area might enable the reward circuitry to influence the immune system.