Date of Award
Bachelor of Science (B.S.) in Biology and University Honors
Matthew G. Drake
Cell receptors, Cellular immunity, Airway (Medicine) -- Physiology -- Effect of Toll-Like Receptor expression on
Background: Toll-like receptor 7 (TLR7) is a single-stranded RNA receptor expressed on airway epithelium that detects respiratory viruses and triggers an immune response. Recently, we found airway sensory nerves also express TLR7, although its role on nerves is unknown.
Objective: To characterize TLR7 expression on airway sensory nerves, and to determine the effects of neuronal TLR7 stimulation.
Methods: Vagal and dorsal root ganglia were isolated from female Hartley guinea pigs (~400g) and fixed in zinc formalin. Nerves were immunolabeled with antibodies against TLR7 and either neurofilament-1(NF-H) to identify A𝛿 fiber sensory nerves or transient receptor potential V1 (TRPV1) to identify C fiber sensory nerves. In separate experiments, dorsal root ganglia were isolated, cultured, and treated with TLR7 agonist R837 (0.1-100microM) for 16 hours. Nerve length, the number of neurites, and the number of branch points were quantified.
Results: Airway sensory nerves originating in the vagal and dorsal root ganglia heterogeneously expressed TLR7. TLR7 was highly expressed on small TRPV1-expressing C fiber neurons, but not large NF-H-positive A𝛿 neurons. TLR7 agonist R837 dose-dependently increased nerve length and branching in vitro.
Conclusions: TLR7 is highly expressed by airway sensory C fibers nerves and its activation stimulates neurite growth. Neuronal TLR7 may facilitate detection of respiratory viruses and regulate anti-viral immune responses.
Funding: NIH grants HL121254, HL 124165, HL113023, AR061567, ES017592, UL1GM118964, and TL4GM118965
Wai, Karol, "Toll-like Receptor 7 Expression and Function on Sensory Nerves" (2018). University Honors Theses. Paper 627.
Available for download on Saturday, June 20, 2020