June 2021
Volume 62, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2021
Nociceptors control innate responses to Pseudomonas aeruginosa
Author Affiliations & Notes
  • Mihaela G Gadjeva
    ID, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Daisy Quellier
    ID, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Jeffrey Lamb
    ID, Brigham and Women's Hospital, Boston, Massachusetts, United States
  • Footnotes
    Commercial Relationships   Mihaela Gadjeva, None; Daisy Quellier, None; Jeffrey Lamb, None
  • Footnotes
    Support  This work is supported by National Institutes of Health RO1 EY022054 to MG.
Investigative Ophthalmology & Visual Science June 2021, Vol.62, 914. doi:
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      Mihaela G Gadjeva, Daisy Quellier, Jeffrey Lamb; Nociceptors control innate responses to Pseudomonas aeruginosa. Invest. Ophthalmol. Vis. Sci. 2021;62(8):914.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : It is not known whether different pathogens induce distinct neuronal responses and how nociceptors affect infection outcomes.

Methods : To monitor nociceptor responses during bacterial infection, C57BL6/N mice were either infected or sham treated, corneal whole mounts harvested at 24h and 48h post-infection, and stained for bIII tubulin and CGRP. To chemically ablate TRPV1+ nociceptors, C57BL6/N mice were treated with three consecutive doses of RTX: 30 ug/kg, 70 ug/kg, and 100 ug/kg subcutaneously. The capsaicin eye wipe test was performed to evaluate functional deficiency of nociceptors. To quantify blink reflexes, mice were monitored using Cochet-Bonnet aesthesiometer. To determine the impact of TRPV1- positive neurons on keratitis susceptibility, RTX-treated mice and vehicle-treated control mice were infected with P. aeruginosa strain 6294 at 5x105 CFU/ml and bacterial burdens were quantified. Myeloid cellular infiltrates were evaluated using CD45, CD11b, Ly6G, ICAM-1 markers using flow cytometry and ImageStream analysis.

Results : Infection induced rapid loss of blink reflexes and collapse of subbasal plexus neuronal fibers. Resiniferatoxin (RTX)-treted mice showed significantly ablated corneal sensory neurons and a temporary mild decrease in blink reflexes, which was recovered. Infected RTX-treated mice exhibited decreased bacterial corneal burdens in the first 24h of infection, elevated myeloid trafficking of CD45+CD11b+Ly6G+ICAM-1- neutrophils and reduced CD45+CD11b+Ly6G+ICAM-1+neutrophils. Mechanistically, increased frequencies of CGRP-induced ICAM-1+ neutrophils in the infected vehicle-treated mice showed reduced neutrophil bactericidal activities.
Infected NaV1.8Cre DTA+ mice, lacking the NaV1.8 channel, showed decreased bacterial burdens at 24h and 48h post-infection, a phenotype which was stronger and more sustained when compared to the RTX-treated mice.

Conclusions : These data showed that sensory neurons can regulate corneal neutrophil responses in a tissue-specific matter affecting disease progression during P. aeruginosa keratitis. Hence, therapeutic modalities that control nociceptor activation could impact anti-infective therapies.

This is a 2021 ARVO Annual Meeting abstract.

 

The image is from an ocular whole mount from infected with P. aeruginosa mouse expressing red fluorescent protein under the NaV 1.8 promoter (Nav 1.8cre/TdTomato). P. aeruginosa 6294-GFP is seen in close proximity of neuronal fibers, suggestive of interactions.

The image is from an ocular whole mount from infected with P. aeruginosa mouse expressing red fluorescent protein under the NaV 1.8 promoter (Nav 1.8cre/TdTomato). P. aeruginosa 6294-GFP is seen in close proximity of neuronal fibers, suggestive of interactions.

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