Mechanisms linking sleep, innate immunity, and neuroinflammation

This narrative review discusses mechanisms underlying bidirectional communication between sleep and the immune system with a focus on innate immune signaling and neuroinflammatory processes. Decades of mechanistic research demonstrate that sleep and immune function are tightly integrated across molecular, cellular, and systems levels. Seminal experiments from the late 1960 s through the early 1980 s established that microbial products, such as muramyl peptides and lipopolysaccharide, along with cytokines including IL-1 and TNF, alter sleep and participate in its physiological regulation. These findings launched contemporary investigations into how innate immune receptors, PAMP recognition, and downstream inflammatory signaling shape sleep-wake architecture. More recent work demonstrates that acute or chronic sleep disruption-including deprivation, restriction, and fragmentation-activates inflammatory signaling pathways, alters cytokine expression, and induces neuroinflammatory responses within the brain. At the cellular level, glial cells play central roles in mediating these effects and linking immune activation to neuronal circuits regulating sleep-wake behavior. Together, these advances reveal that sleep-immune interactions are deeply integrated and critical for maintaining health.