Brain motor and fear circuits regulate leukocytes during acute stress

Wolfram C. Poller, Jeffrey Downey, Agnes A. Mooslechner, Nargis Khan, Long Li, Christopher T. Chan, Cameron S. McAlpine, Chunliang Xu, Florian Kahles, Shun He, Henrike Janssen, John E. Mindur, Sumnima Singh, Máté G. Kiss, Laura Alonso-Herranz, Yoshiko Iwamoto, Rainer H. Kohler, Lai Ping Wong, Kashish Chetal, Scott J. RussoRuslan I. Sadreyev, Ralph Weissleder, Matthias Nahrendorf, Paul S. Frenette, Maziar Divangahi, Filip K. Swirski

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The nervous and immune systems are intricately linked1. Although psychological stress is known to modulate immune function, mechanistic pathways linking stress networks in the brain to peripheral leukocytes remain poorly understood2. Here we show that distinct brain regions shape leukocyte distribution and function throughout the body during acute stress in mice. Using optogenetics and chemogenetics, we demonstrate that motor circuits induce rapid neutrophil mobilization from the bone marrow to peripheral tissues through 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 through direct, cell-intrinsic glucocorticoid signalling. These stress-induced, counter-directional, population-wide leukocyte shifts are associated with altered disease susceptibility. On the one hand, acute stress changes innate immunity by reprogramming neutrophils and directing their recruitment to sites of injury. On the other hand, corticotropin-releasing hormone neuron-mediated leukocyte shifts protect against the acquisition of autoimmunity, but impair immunity to SARS-CoV-2 and influenza infection. Collectively, these data show that distinct brain regions differentially and rapidly tailor the leukocyte landscape during psychological stress, therefore calibrating the ability of the immune system to respond to physical threats.

Original languageEnglish
Pages (from-to)578-584
Number of pages7
JournalNature
Volume607
Issue number7919
DOIs
StatePublished - 21 Jul 2022

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