In:
PLOS Pathogens, Public Library of Science (PLoS), Vol. 17, No. 5 ( 2021-5-6), p. e1009557-
Abstract:
We report a rapid reduction in blink reflexes during in vivo ocular Pseudomonas aeruginosa infection, which is commonly attributed and indicative of functional neuronal damage. Sensory neurons derived in vitro from trigeminal ganglia (TG) were able to directly respond to P . aeruginosa but reacted significantly less to strains of P . aeruginosa that lacked virulence factors such as pili, flagella, or a type III secretion system. These observations led us to explore the impact of neurons on the host’s susceptibility to P . aeruginosa keratitis. Mice were treated with Resiniferatoxin (RTX), a potent activator of Transient Receptor Potential Vanilloid 1 (TRPV1) channels, which significantly ablated corneal sensory neurons, exhibited delayed disease progression that was exemplified with decreased bacterial corneal burdens and altered neutrophil trafficking. Sensitization to disease was due to the increased frequencies of CGRP-induced ICAM-1 + neutrophils in the infected corneas and reduced neutrophil bactericidal activities. These data showed that sensory neurons regulate corneal neutrophil responses in a tissue-specific matter affecting disease progression during P . aeruginosa keratitis. Hence, therapeutic modalities that control nociception could beneficially impact anti-infective therapy.
Type of Medium:
Online Resource
ISSN:
1553-7374
DOI:
10.1371/journal.ppat.1009557
DOI:
10.1371/journal.ppat.1009557.g001
DOI:
10.1371/journal.ppat.1009557.g002
DOI:
10.1371/journal.ppat.1009557.g003
DOI:
10.1371/journal.ppat.1009557.g004
DOI:
10.1371/journal.ppat.1009557.g005
DOI:
10.1371/journal.ppat.1009557.g006
DOI:
10.1371/journal.ppat.1009557.g007
DOI:
10.1371/journal.ppat.1009557.g008
DOI:
10.1371/journal.ppat.1009557.s001
DOI:
10.1371/journal.ppat.1009557.s002
DOI:
10.1371/journal.ppat.1009557.s003
DOI:
10.1371/journal.ppat.1009557.s004
DOI:
10.1371/journal.ppat.1009557.s005
DOI:
10.1371/journal.ppat.1009557.s006
DOI:
10.1371/journal.ppat.1009557.s007
DOI:
10.1371/journal.ppat.1009557.s008
DOI:
10.1371/journal.ppat.1009557.s009
DOI:
10.1371/journal.ppat.1009557.s010
DOI:
10.1371/journal.ppat.1009557.s011
DOI:
10.1371/journal.ppat.1009557.s012
DOI:
10.1371/journal.ppat.1009557.r001
DOI:
10.1371/journal.ppat.1009557.r002
DOI:
10.1371/journal.ppat.1009557.r003
DOI:
10.1371/journal.ppat.1009557.r004
DOI:
10.1371/journal.ppat.1009557.r005
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2021
detail.hit.zdb_id:
2205412-1
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