Fig 8. Schematic model depicting the impact of neuronal regulation on P. aeruginosa induced keratitis.

P. aeruginosa utilizes flagella, pili, and type III secretion systems to initiate neuronal activation. As a result, the threshold of activation of Transient Receptor Potential Cation Channel, subfamily V, member 1 (TRPV1) is reduced increasing the excitability of the peripheral terminal membrane. When a threshold of depolarization is reached, voltage-gated sodium channels (e.g., NaV1.8) are activated and an action potential is produced and is propagated along the axon. An influx of calcium through voltage-gated calcium channels (VGCC) triggers the release of neuropeptides including calcitonin-gene-related protein (CGRP), which controls myeloid responses in the corneas. CGRP inhibits myeloid infiltration to the tissues and alters myeloid phenotypes in response to infection. The ICAM-1⁺ Ly6G⁺ CD11b⁺ neutrophils have decreased ability to kill bacteria.