Balancing inflammation under stress: glucocorticoid regulation of innate immune pathways

Abstract Despite our constant exposure to potential dangers, our ability to withstand infection and tissue damage relies on a network of coordinated cellular security systems. One of these security features is our innate immune system, which senses danger signals from invading pathogens as well as host-derived stress signals while remaining largely unresponsive to normal host molecules and the flora of the host microbiota. This intertwining network of cellular guardians expresses pattern recognition receptors to recognise specifically pathogen-associated molecular patterns and danger-associated molecular patterns and elicit an inflammatory response. Inflammation is an integral process to eliminate a pathogenic threat while simultaneously promoting tissue repair. However, a balance exists, and persistent or aberrant inflammation can instead drive tissue damage and disease. To douse inflammatory flames, the endocrine system releases endogenous glucocorticoids, which possess potent immunomodulatory actions. This review will explore the cross-talk between endogenous glucocorticoid signalling and innate immune signalling pathways