GSE201391
Brain motor and fear circuits differentially regulate leukocyte distribution and function during acute stress [single-cell RNA-seq]
The nervous and immune systems are intricately linked. Although psychological stress is known to affect immune function, direct mechanistic pathways linking stress networks in the brain to peripheral leukocytes remain poorly understood. Here, we show that distinct brain regions shape leukocyte distribution throughout the body during acute stress in mice. Using optogenetics and chemogenetics, we demonstrate that the motor cortex induces rapid neutrophil mobilization to peripheral tissues via skeletal muscle-derived neutrophil-attracting chemokines. Conversely, the paraventricular hypothalamus controls monocyte and lymphocyte egress from secondary lymphoid organs and blood to the bone marrow via direct and cell-intrinsic glucocorticoid signaling. These stress-induced counter-directional and population-wide leukocyte shifts are associated with altered disease susceptibility. On the one hand, acute stress changes innate immunity by reprogramming neutrophils and precipitating their recruitment to atherosclerotic plaques. On the other hand, stress-induced leukocyte shifts impair adaptive immunity, increasing susceptibility to SARS-Cov-2 and influenza infection but protecting against autoimmunity in a model of multiple sclerosis. Collectively, these data show that distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, thus calibrating the immune system's capacity to respond to physical threats. Overall design: We FACS sorted blood neutrophils (CD45+;LIN-;CD11b+;Ly-6G+) from wild type mice under three different conditions: 1. relaxed; 2. 1h restraint stressed; 3. 1h restraint stressed followed by 3 hours of recovery