Developmental Time Course of Innate Immune Response to Peripheral Sensory Denervation in the Trigeminal and Gustatory System

Few sensory modalities engage in cross-modal interactions within the peripheral nervous system, making the apparent integrated relationship between the gustatory and trigeminal systems in the anterior tongue particularly intriguing. The effects of gustatory chorda tympani nerve transection in rats (CTX) lead to well-documented reductions in taste bud size and anatomical changes to the surrounding lingual epithelium, particularly when injury occurs early in life. We tested the inverse of this relationship, removing lingual nerve input while leaving the chorda intact. Rats underwent lingual transection (LX) during neonatal, juvenile or adult ages (10, 25, or 65 days of age, respectively), and anatomical outcomes were assessed following various survival times. Results indicate that LX impacts taste receptor cells and alters epithelial morphology of fungiform papillae, especially during early development. These findings highlight dual roles for the lingual nerve in the maintenance of both gustatory and non-gustatory tissues on the anterior tongue. The mechanism for these cross-modal changes is unknown, as neither the lingual nor the chorda tympani nerves innervate cells of the opposing system. The innate immune system has been suggested as a mediating factor between the two sensory systems. In order to explore this hypothesis we evaluated the response of neutrophils, the most abundant leukocyte in the mammalian immune system, after CTX or LX. We quantified myeloperoxidase-positive cells in neonatal, juvenile, or adult animals at 12, 24, or 48 hours after surgery . CTX and LX denervation each resulted in a significant increase in the number of neutrophils observed within 12 hours of injury in neonatal animals, and these differences were less apparent following surgery at older ages. Thus, the neutrophil response to nerve injury appears to mirror the developmental pattern of severity observed in anatomical studies. In total, these results provide the first examination of the effects of lingual nerve transection on the anterior tongue. They provide strong evidence of a multimodal, inter-sensory system that varies by developmental stage and is---at least in part---mediated by neutrophils, the largest component of the innate immune system.