The carotid body in sepsis: From homeostatic defense to immunometabolic dysregulation.

Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection and involves failure of immune, metabolic, respiratory, cardiovascular, thermal, endocrine, and autonomic regulation. In this review, we propose that the carotid body may act as a peripheral interoceptive checkpoint in the transition from adaptive host defense to immunometabolic decompensation. The discussion is organized around four interconnected dimensions. First, we examine inflammatory and metabolic signals that may be detected by the carotid body during sepsis, including cytokines, lactate, glucose, hypoxemia, acid-base disturbances, and other energetic stress signals. Second, we discuss the respiratory consequences of carotid body activation or dysfunction, with emphasis on ventilation, hypoxic chemosensitivity, and ventilatory responses during systemic inflammation. Third, we address cardiovascular and autonomic consequences, including sympathetic activation, vascular tone, arterial pressure, organ perfusion, and recruitment of the splanchnic anti-inflammatory pathway. Fourth, we consider inflammation-induced carotid body remodeling and the resulting loss of sensory fidelity. Experimental evidence indicates that circulating TNF-α activates carotid body afferents and recruits sympathetic anti-inflammatory pathways, whereas severe or persistent inflammation can alter carotid body structure, chemosensory gain, and afferent output. Although direct clinical evidence remains limited, this framework identifies the carotid body as a testable neuroimmune interface. Early stimulus-coupled activation may support respiratory, cardiovascular, autonomic, metabolic, and immune adaptation, whereas persistent inflammation may produce elevated tonic afferent activity, reduced stimulus-evoked responsiveness, and impaired sensory discrimination.