Universität zu Köln

Lin, Tiffany ORCID: 0000-0001-9829-2045, Quellier, Daisy ORCID: 0000-0003-0999-8965, Lamb, Jeffrey, Voisin, Tiphaine, Baral, Pankaj ORCID: 0000-0002-3902-2368, Bock, Felix, Schoenberg, Alfrun, Mirchev, Rossen, Pier, Gerald ORCID: 0000-0002-9112-2331, Chiu, Isaac and Gadjeva, Mihaela (2021). Pseudomonas aeruginosa-induced nociceptor activation increases susceptibility to infection. PLoS Pathog., 17 (5). SAN FRANCISCO: PUBLIC LIBRARY SCIENCE. ISSN 1553-7374

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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. Author summary Many of the molecular mechanisms behind bacterial keratitis induced nociception activation and specifically, how pathogen-sensing sensory neurons impact the outcome of infection have yet to be discovered, Elucidating the molecular and cellular mechanisms of nociceptor activation during bacterial keratitis can have a profound impact on treatment approaches. In this study, we established that P. aeruginosa can directly induce calcium influx in neurons and this induction is dependent on several virulence factors. Further, we demonstrated that Resiniferatoxin (RTX), a toxin that overactivates TRPV1 channels leading to chemical ablation of neurons, induces significant loss of sensory neurons in the cornea and this improves temporarily local innate responses to P. aeruginosa.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Lin, Tiffany UNSPECIFIED orcid.org/0000-0001-9829-2045 UNSPECIFIED Quellier, Daisy UNSPECIFIED orcid.org/0000-0003-0999-8965 UNSPECIFIED Lamb, Jeffrey UNSPECIFIED UNSPECIFIED UNSPECIFIED Voisin, Tiphaine UNSPECIFIED UNSPECIFIED UNSPECIFIED Baral, Pankaj UNSPECIFIED orcid.org/0000-0002-3902-2368 UNSPECIFIED Bock, Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Schoenberg, Alfrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Mirchev, Rossen UNSPECIFIED UNSPECIFIED UNSPECIFIED Pier, Gerald UNSPECIFIED orcid.org/0000-0002-9112-2331 UNSPECIFIED Chiu, Isaac UNSPECIFIED UNSPECIFIED UNSPECIFIED Gadjeva, Mihaela UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-580513
DOI:	10.1371/journal.ppat.1009557
Journal or Publication Title:	PLoS Pathog.
Volume:	17
Number:	5
Date:	2021
Publisher:	PUBLIC LIBRARY SCIENCE
Place of Publication:	SAN FRANCISCO
ISSN:	1553-7374
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language VIVO-CONFOCAL-MICROSCOPY; NERVE ALTERATIONS; FUNGAL KERATITIS; SENSORY NEURONS; MOUSE; ADHERENCE; SENSATION; PAIN; INFLAMMATION; INNERVATION Multiple languages Microbiology; Parasitology; Virology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58051