# The production of the chemokine CCL2 by corneal sensory neurons initiates anti-viral immunity at the cornea and trigeminal ganglion

## TL;DR

Corneal sensory neurons produce CCL2, which helps recruit immune cells to fight viral infections in the eye and trigeminal ganglion.

## Contribution

This study reveals a novel role of corneal afferents in initiating anti-viral immunity through CCL2 production.

## Key findings

- Optogenetic activation of corneal afferents increases immune cell recruitment to the cornea and trigeminal ganglion.
- Neuron-derived CCL2 is critical for immune cell recruitment during HSV-1 infection.
- Deleting neuronal CCL2 impairs early viral control and immune cell responses.

## Abstract

The cornea is an epithelial tissue densely innervated by sensory neurons but devoid of autonomic innervation, lymphatics, and vasculature. The simplicity of the cellular composition suggests that corneal afferents participate in tissue homeostasis by regulating immune cells. Transcriptomic analysis of retrogradely labeled corneal afferents in the trigeminal ganglion (TG) found that they express many immune-relatedgenes.Optogeneticactivation of corneal afferents increased neutrophils and monocytes in both the cornea and TG, as well as inducing phenotypic changes in natural killer (NK) cells. Unsupervised pathway analysis indicated neuronally expressed Ccl2 as a modulator of immune cell responses. Selective deletion of neuronal Ccl2 decreased the number of myeloid cells in the cornea and TG in response to herpes simplex virus (HSV) infection, resulting in compromised viral clearance during primary infection. These experiments demonstrate that corneal afferent activation is sufficient to trigger inflammatory responses that can assist the host in initiating anti-viral immunity.

Yun et al. combined neuronal labeling, single-cell transcriptomics, and computational analyses to map communication between corneal neurons and immune cells. They identified neuron-derived CCL2 as recruiting immune cells during early HSV-1 infection, and loss of CCL2 reduced immune recruitment, impairing early viral control.