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Sensory neurons derived<jats:italic>in vitro<\/jats:italic>from trigeminal ganglia (TG) were able to directly respond to<jats:italic>P<\/jats:italic>.<jats:italic>aeruginosa<\/jats:italic>but reacted significantly less to strains of<jats:italic>P<\/jats:italic>.<jats:italic>aeruginosa<\/jats:italic>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\u2019s susceptibility to<jats:italic>P<\/jats:italic>.<jats:italic>aeruginosa<\/jats:italic>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<jats:sup>+<\/jats:sup>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<jats:italic>P<\/jats:italic>.<jats:italic>aeruginosa<\/jats:italic>keratitis. Hence, therapeutic modalities that control nociception could beneficially impact anti-infective therapy.<\/jats:p>","DOI":"10.1371\/journal.ppat.1009557","type":"journal-article","created":{"date-parts":[[2021,5,6]],"date-time":"2021-05-06T17:31:16Z","timestamp":1620322276000},"page":"e1009557","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":29,"title":["Pseudomonas aeruginosa\u2013induced nociceptor activation increases susceptibility to infection"],"prefix":"10.1371","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9829-2045","authenticated-orcid":true,"given":"Tiffany","family":"Lin","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0999-8965","authenticated-orcid":true,"given":"Daisy","family":"Quellier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey","family":"Lamb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0643-5948","authenticated-orcid":true,"given":"Tiphaine","family":"Voisin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3902-2368","authenticated-orcid":true,"given":"Pankaj","family":"Baral","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix","family":"Bock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5660-9072","authenticated-orcid":true,"given":"Alfrun","family":"Sch\u00f6nberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rossen","family":"Mirchev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9112-2331","authenticated-orcid":true,"given":"Gerald","family":"Pier","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Isaac","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-386X","authenticated-orcid":true,"given":"Mihaela","family":"Gadjeva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,5,6]]},"reference":[{"key":"ppat.1009557.ref001","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1186\/1756-0500-7-907","article-title":"Pseudomonas aeruginosa keratitis misdiagnosed as fungal keratitis by in vivo confocal microscopy: a case report","volume":"7","author":"J Hong","year":"2014","journal-title":"BMC Res Notes"},{"key":"ppat.1009557.ref002","article-title":"V. 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