Nerve‐associated transient receptor potential ion channels can contribute to intrinsic resistance to bacterial adhesion in vivo

• DOI: 10.1096/fj.202100874r
• Publication Date: 2021-09-28T00:03:36Z
• Authors: Stephanie J. Wan; Ananya Datta; Orneika Flandrin; Matteo M. E. Metr...; Sophia Ma; Vincent Nieto; Abby R. Kroken; Rose Z. Hill; Diana M. Bautista; David J. Evans; Suzanne M. J. Fle...
• Keywords: Knockout mouse; TRPM8

The cornea of the eye differs from other mucosal surfaces in that it lacks a viable bacterial microbiome and by its unusually high density sensory nerve endings. Here, we explored role corneal nerves preventing adhesion. Pharmacological genetic methods were used to inhibit function or their associated transient receptor potential cation channels TRPA1 TRPV1. Impacts on adhesion, resident immune cells, epithelial integrity examined using fluorescent labeling quantitative confocal imaging. TRPA1/TRPV1 double gene-knockout mice more susceptible adhesion environmental bacteria deliberately-inoculated Pseudomonas aeruginosa. Supporting involvement TRPA1/TRPV1-expressing nerves, P. aeruginosa was also promoted treatment with bupivacaine, ablation RTX. Moreover, TRPA1/TRPV1-dependent defense abolished enucleation which severs nerves. High-resolution imaging showed normal ultrastructure surface-labeling wheat-germ agglutinin for knockout murine corneas, intact barrier absence fluorescein staining. adhering corneas after perturbation failed penetrate surface. Single roles both TRPV1, TRPA1-/- while TRPV1-/- instead accumulated bacteria. Corneal CD45+/CD11c+ cell responses challenge, previously shown counter depended Together, these results demonstrate resistance vivo suggest mechanisms involve populations.