Immunomodulation of gut-brain interactions

How does the brain interpret signals from the body, and how do peripheral systems respond to brain signals? A fundamental function of central nervous systems in all animals is their ability to sense and integrate information from the environment. Equally important but much less understood is the brain’s ability to perceive information from inside the body. We propose to study the bidirectional interaction between body and brain from the perspective of the immune system. This interplay is particularly relevant in the context of sickness behavior. Immune responses to infections in the body affect the brain and result in increased sleep and fatigue. Conversely, neuronal circuits in the brain send signals to peripheral organs and orchestrate immune responses. However, many aspects of these interactions remain mysterious, and fatigue associated with chronic infections or post-infection syndromes, such as Long COVID, is a major health concern. We propose to study body-brain communication with a particular focus on gastrointestinal infection. We will (i) determine how peripheral infection triggers signals from the gut that affect sleep behavior; (ii) study how neuronal gut-brain signals influence brain states regulating arousal and fatigue; and (iii) interrogate neuronal pathways emanating from brain structures that modulate immune responses to infection in the gut. Collectively, these aims will enhance our understanding of neuroimmune connections and will serve as a blueprint for the systematic interrogation of body-brain circuits through interactions between groups at Wu Tsai and the broader Stanford community.