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

Wan, Stephanie; Datta, Amit; Flandrin, Orneika; Metruccio, Matteo M. E.; Ma, Sophia; Nieto, Vincent; Kroken, Abby R.; Hill, Rose Z.; Bautista, Diana M.; Evans, David J.; Fleiszig, Suzanne M. J.

doi:10.1096/fj.202100874r

Cited by 6 publications

(12 citation statements)

References 77 publications

(248 reference statements)

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“…L-carnitine (1 mmol/L) was already shown to suppress TRPV1 functional expression in excitable corneal nociceptive innervated neurons [38][39][40]. Our current study is unique since either 1 or 3 mmol/L of L-carnitine blocked each of the three different hallmarks of TRPV1 activation in HCE-T cells, as illustrated in Figure 5.…”

Section: Modes Of Suppression Of Trpv1 Activation By L-carnitinementioning

confidence: 52%

L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells

Lucius,

Chhatwal,

Valtink

et al. 2023

IJMS

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Tear film hyperosmolarity induces dry eye syndrome (DES) through transient receptor potential vanilloid type 1 (TRPV1) activation. L-carnitine is a viable therapeutic agent since it protects against this hypertonicity-induced response. Here, we investigated whether L-carnitine inhibits TRPV1 activation by blocking heat- or capsaicin-induced increases in Ca2+ influx or hyperosmotic stress-induced cell volume shrinkage in a human corneal epithelial cell line (HCE-T). Single-cell fluorescence imaging of calcein/AM-loaded cells or fura-2/AM-labeled cells was used to evaluate cell volume changes and intracellular calcium levels, respectively. Planar patch-clamp technique was used to measure whole-cell currents. TRPV1 activation via either capsaicin (20 µmol/L), hyperosmolarity (≈450 mosmol/L) or an increase in ambient bath temperature to 43 °C induced intracellular calcium transients and augmented whole-cell currents, whereas hypertonicity induced cell volume shrinkage. In contrast, either capsazepine (10 µmol/L) or L-carnitine (1–3 mmol/L) reduced all these responses. Taken together, L-carnitine and capsazepine suppress hypertonicity-induced TRPV1 activation by blocking cell volume shrinkage.

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Section: Modes Of Suppression Of Trpv1 Activation By L-carnitinementioning

confidence: 52%

L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells

Lucius,

Chhatwal,

Valtink

et al. 2023

IJMS

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“…in the ocular microenvironment, and these data were supported by other studies. 35 , 36 In these studies, C. mast exhibited a filamentous form suggestive of defined colonization and adherence to ocular tissue. Here, we were able to use live in vivo imaging to conclude that mCherry + C. mast does not reside in the cornea or the limbal region of the eye.…”

Section: Discussionmentioning

confidence: 81%

Genetic Manipulation of Corynebacterium mastitidis to Better Understand the Ocular Microbiome

Rigas

Treat

Shane

et al. 2023

Invest. Ophthalmol. Vis. Sci.

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Purpose Corynebacterium spp. are Gram-positive bacteria commonly associated with the ocular surface. Corynebacterium mastitidis was isolated from mouse eyes and was demonstrated to induce a beneficial immune response that can protect the eye from pathogenic infection. Because eye-relevant Corynebacterium spp. are not well described, we generated a C. mast transposon (Tn) mutant library to gain a better understanding of the nature of eye-colonizing bacteria. Methods Tn mutagenesis was performed with a custom Tn5-based transposon that incorporated a promoterless gene for the fluorescent protein mCherry. We screened our library using flow cytometry and enzymatic assays to identify useful mutants that demonstrate the utility of our approach. Results Fluorescence-activated cell sorting (FACS) of mCherry + bacteria allowed us to identify a highly fluorescent mutant that was detectable on the murine ocular surface using microscopy. We also identified a functional knockout that was unable to hydrolyze urea, Urease KO . Although uric acid is an antimicrobial factor produced in tears, Urease KO bacterium maintained an ability to colonize the eye, suggesting that urea hydrolysis is not required for colonization. In vitro and in vivo, both mutants maintained the potential to stimulate protective immunity as compared to wild-type C. mast . Conclusions In sum, we describe a method to genetically modify an eye-colonizing microbe, C. mast. Furthermore, the procedures outlined here will allow for the continued development of genetic tools for modifying ocular Corynebacterium spp., which will lead to a more complete understanding of the interactions between the microbiome and host immunity at the ocular surface.

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“…At the ocular surface, TRPV1 expression is upregulated after corneal injury 168 . Furthermore, activation of the nociceptive receptor, TRPV1, resulted in increased susceptibility to Pseudomonas aeruginosa infection 157 ; however, TRPV1 signaling also appears to appear to prevent the adhesion of environmental bacteria 169 .…”

Section: Neuroimmune Axis and The Modulation Of Mucosal Immunitymentioning

confidence: 99%

Mucosal immunology of the ocular surface

Paiva

Leger²,

Caspi³

2022

Mucosal Immunology

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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.

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

Cited by 6 publications

References 77 publications

L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells

L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells

Genetic Manipulation of Corynebacterium mastitidis to Better Understand the Ocular Microbiome

Mucosal immunology of the ocular surface

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