Brain motor and fear circuits regulate leukocytes during acute stress

Stress and immunity — the circuit makes the difference

“…The intersection between immune and stress systems has been studied extensively, but our understanding of how stress-specific brain circuits affect discrete elements of the immune system, and how this could impact the body's ability to respond to various immune challenges is very limited. A new study by Poller et al 1 published in Nature provides mechanistic insights into how acute stress uses distinct brain circuits to regulate leukocyte dynamics and contribute to differential disease susceptibility in response to either autoimmune challenge or viral infection.…”

“…Although key stress hormones such as norepinephrine and glucocorticoids have been implicated in these processes, a direct link between the brain cells that coordinate the neuroendocrine stress response has remained elusive. Poller et al 1 now provide insights into distinct signaling mechanisms that control the rapid mobilization of neutrophils into the circulation, followed by a slow movement of monocytes and lymphocytes from peripheral organs to the bone marrow after acute stress 1 (Fig. 1).…”

“…These cells release CRH to initiate a cascade of peripheral signals that culminate in an increase in circulating glucocorticoids. Poller et al 1 propose that glucocorticoids act in a leukocyte-autonomous fashion to enhance the function of CXC chemokine receptor 4 (CXCR4). CXCR4 has previously been described as a key player in the homing of cells to the bone marrow.…”

“…This increase in leukocyte sequestration into the bone marrow has opposing effects on how the body responds to an autoimmune challenge versus a viral challenge. By subjecting acutely stressed and unstressed mice to experimental autoimmune encephalomyelitis (EAE), Poller et al 1 show that stressed mice have lower clinical severity scores. These effects, which suggest mice are protected from disease initiation and progression, require the activation of CRH neurons and the actions of circulating corticosterone.…”

“…The results are quite different when the system is challenged with a virus. Given the pandemic, this is particularly topical, so Poller et al 1 examined the effects of acute stress on viral infections. In comparison to age-and sex-matched controls exposed to SARS-CoV-2, stressed mice exposed to SARS-CoV-2 had higher viral titers.…”