The ability of a mammalian host to sense and defend against pathogens is essential for survival. Recent studies suggest that the sensory nervous system plays a crucial role in host immunity. Sensory neurons extend afferent projections throughout the body, allowing them to rapidly detect and respond to threats and relay signals to the central nervous system (CNS) [1]. Sensory neurons detect a broad array of chemical, thermal, and mechanical stimuli through specialized ion channels, such as PIEZO2, TRPV1, and TRPA1, and voltage-gated ion channels, such as NaV1.8 and NaV1.9 [1]. They mediate protective sensations such as pain and itch and directly communicate with immune cells via neurotransmitters and neuropeptides [2].

In this review, we discuss the role of sensory neurons in pathogen detection, immune modulation, and behavioral reflexes, as well as how their interactions with the CNS impact tissue immunity. Understanding the multifaceted roles of sensory neurons in pathogen defense may reveal novel approaches to treating infectious diseases.