12. Exposure to acute stress modifies plasma exosomes capable of improving host defense to bacterial challenge

Exosomes, biologically active nanoparticles (40–100 nm) released by hematopoietic and non-hematopoietic cells, contain a variety of proteins and small, non-coding RNA known as microRNA (miRNA). Exposure to various pathogens and disease states modifies the composition and function of exosomes, but recent studies reveal that the acute stress response can also evoke in vivo exosomal changes in the absence of disease. The present study demonstrates that exposing male Fisher 344 rats to an acute stressor modulates proteins and miRNA in their circulating plasma exosomes, specifically up-regulating heat shock protein 72 (Hsp72) and decreasing miR-142-5p and −203 expression. The selected miRNAs and Hsp72 are associated with immunomodulatory functions and are likely a critical component of stress-enhanced immunity. Further, we demonstrate that some of these stress-induced modifications in plasma exosomes are mediated by sympathetic nervous system (SNS) activation of alpha-1 adrenergic receptors (ADRs), since drug-mediated blockade of the receptors significantly attenuates the stress-induced modifications of exosomal Hsp72 and miR-142-5p. Moreover, in vivo analysis reveals that administering rats stress modified plasma exosomes improves their inflammatory response to subcutaneous injections of Escherichia coli ( E. coli ) compared to rats administered non-stressed plasma exosomes or saline. Together, these findings suggest that activation of the acute stress response potentiates innate immunity by modifying the proteomic and miRNA profile of exosomes released into the circulation. Supported by NSF IOS 1022451.