Pseudomonas aeruginosa–induced nociceptor activation increases susceptibility to infection

Lin, Tiffany; Quellier, Daisy; Lamb, Jeffrey; Voisin, Tiphaine; Baral, Pankaj; Bock, Felix; Schönberg, Alfrun; Mirchev, Rossen; Pier, Gerald B.; Chiu, Isaac M.; Gadjeva, Mihaela

doi:10.1371/journal.ppat.1009557

Cited by 23 publications

(16 citation statements)

References 65 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…42 It was also more recently shown that during P. aeruginosa infection of the cornea, inflammation is promoted by TRPV1, associated with CGRP-mediated recruitment of neutrophils with reduced bactericidal activity. 53 Clearly, the role(s) of TRPA1 and TRPV1 nociceptors in modulating progression of infection and associated disease pathology via immune cell recruitment/function is complex and further studies will help elucidate tissue and/or pathogen specificity of their involvement.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

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

show abstract

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Corneal nerve density was determined as described before with minor modifications. 34 , 35 Briefly, Z-stack images were acquired from the central and pericentral regions of the cornea (∼500 µm 2 /area) with a comparable thickness (∼50 µm) using the TCS SP8 laser confocal microscope. The images were collapsed to two dimensions and converted to a binary image using ImageJ 1.52p (National Institutes of Health, Bethesda, MD, USA).…”

Section: Methodsmentioning

confidence: 99%

Prophylactic Knockdown of the miR-183/96/182 Cluster AmelioratesPseudomonas aeruginosa–Induced Keratitis

McClellan

Pitchaikannu

Wright

et al. 2021

Invest. Ophthalmol. Vis. Sci.

View full text Add to dashboard Cite

Purpose Previously, we demonstrated that miR-183/96/182 cluster (miR-183C) knockout mice exhibit decreased severity of Pseudomonas aeruginosa (PA)-induced keratitis. This study tests the hypothesis that prophylactic knockdown of miR-183C ameliorates PA keratitis indicative of a therapeutic potential. Methods Eight-week-old miR-183C wild-type and C57BL/6J inbred mice were used. Locked nucleic acid–modified anti-miR-183C or negative control oligoribonucleotides with scrambled sequences (NC ORNs) were injected subconjunctivally 1 day before and then topically applied once daily for 5 days post-infection (dpi) (strain 19660). Corneal disease was graded at 1, 3, and 5 dpi. Corneas were harvested for RT-PCR, ELISA, immunofluorescence (IF), myeloperoxidase and plate count assays, and flow cytometry. Corneal nerve density was evaluated in flatmounted corneas by IF staining with anti-β-III tubulin antibody. Results Anti-miR-183C downregulated miR-183C in the cornea. It resulted in an increase in IL-1β at 1 dpi, which was decreased at 5 dpi; fewer polymorphonuclear leukocytes (PMNs) at 5 dpi; lower viable bacterial plate count at both 1 and 5 dpi; increased percentages of MHCII + macrophages (Mϕ) and dendritic cells (DCs), consistent with enhanced activation/maturation; and decreased severity of PA keratitis. Anti-miR-183C treatment in the cornea of naïve mice resulted in a transient reduction of corneal nerve density, which was fully recovered one week after the last anti-miR application. miR-183C targets repulsive axon-guidance receptor molecule Neuropilin 1, which may mediate the effect of anti-miR-183C on corneal nerve regression. Conclusions Prophylactic miR-183C knockdown is protective against PA keratitis through its regulation of innate immunity, corneal innervation, and neuroimmune interactions.

show abstract

“…Calcitonin gene-related peptide (CGRP) is another factor that influences corneal homeostasis by increasing wound healing and promoting tissue healing phenotypes in macrophages (M2) 154 , 155 . Conversely, CGRP is also known to play a role in photophobia and may limit the ability of the cornea to resist infection 156 , 157 . Vasoactive intestinal peptide (VIP) is another neuropeptide produced at the ocular surface, and this factor has been shown to aid in limiting disease in diabetic keratopathy, bacterial keratitis, and allergic conjunctivitis 158 – 161 .…”

Section: Neuroimmune Axis and The Modulation Of Mucosal Immunitymentioning

confidence: 99%

Mucosal immunology of the ocular surface

Paiva

Leger²,

Caspi³

2022

Mucosal Immunology

View full text Add to dashboard Cite

The eye is a sensory organ exposed to the environment and protected by a mucosal tissue barrier. While it shares a number of features with other mucosal tissues, the ocular mucosal system, composed of the conjunctiva, Meibomian glands, and lacrimal glands, is specialized to address the unique needs of (a) lubrication and (b) host defense of the ocular surface. Not surprisingly, most challenges, physical and immunological, to the homeostasis of the eye fall into those two categories. Dry eye, a dysfunction of the lacrimal glands and/or Meibomian glands, which can both cause, or arise from, sensory defects, including those caused by corneal herpes virus infection, serve as examples of these perturbations and will be discussed ahead. To preserve vision, dense neuronal and immune networks sense various stimuli and orchestrate responses, which must be tightly controlled to provide protection, while simultaneously minimizing collateral damage. All this happens against the backdrop of, and can be modified by, the microorganisms that colonize the ocular mucosa long term, or that are simply transient passengers introduced from the environment. This review will attempt to synthesize the existing knowledge and develop trends in the study of the unique mucosal and immune elements of the ocular surface.

show abstract

Pseudomonas aeruginosa–induced nociceptor activation increases susceptibility to infection

Cited by 23 publications

References 65 publications

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

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

Prophylactic Knockdown of the miR-183/96/182 Cluster AmelioratesPseudomonas aeruginosa–Induced Keratitis

Mucosal immunology of the ocular surface

Contact Info

Product

Resources

About