PMID- 33956874
OWN - NLM
STAT- MEDLINE
DCOM- 20211004
LR  - 20211004
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 17
IP  - 5
DP  - 2021 May
TI  - Pseudomonas aeruginosa-induced nociceptor activation increases susceptibility to 
      infection.
PG  - e1009557
LID - 10.1371/journal.ppat.1009557 [doi]
LID - e1009557
AB  - 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.
FAU - Lin, Tiffany
AU  - Lin T
AUID- ORCID: 0000-0001-9829-2045
AD  - Department of Medicine, Division of Infectious Diseases, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, Massachusetts, United States of 
      America.
FAU - Quellier, Daisy
AU  - Quellier D
AUID- ORCID: 0000-0003-0999-8965
AD  - Department of Medicine, Division of Infectious Diseases, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, Massachusetts, United States of 
      America.
FAU - Lamb, Jeffrey
AU  - Lamb J
AD  - Department of Medicine, Division of Infectious Diseases, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, Massachusetts, United States of 
      America.
FAU - Voisin, Tiphaine
AU  - Voisin T
AUID- ORCID: 0000-0003-0643-5948
AD  - Department of Immunology, Harvard Medical School, Boston, Massachusetts, United 
      States of America.
FAU - Baral, Pankaj
AU  - Baral P
AUID- ORCID: 0000-0002-3902-2368
AD  - Department of Immunology, Harvard Medical School, Boston, Massachusetts, United 
      States of America.
FAU - Bock, Felix
AU  - Bock F
AD  - Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
FAU - Schonberg, Alfrun
AU  - Schonberg A
AUID- ORCID: 0000-0002-5660-9072
AD  - Department of Ophthalmology, University Hospital of Cologne, Cologne, Germany.
FAU - Mirchev, Rossen
AU  - Mirchev R
AD  - Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical 
      School, Boston, Massachusetts, United States of America.
FAU - Pier, Gerald
AU  - Pier G
AUID- ORCID: 0000-0002-9112-2331
AD  - Department of Medicine, Division of Infectious Diseases, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, Massachusetts, United States of 
      America.
FAU - Chiu, Isaac
AU  - Chiu I
AD  - Department of Immunology, Harvard Medical School, Boston, Massachusetts, United 
      States of America.
FAU - Gadjeva, Mihaela
AU  - Gadjeva M
AUID- ORCID: 0000-0002-9014-386X
AD  - Department of Medicine, Division of Infectious Diseases, Brigham and Women's 
      Hospital, Harvard Medical School, Boston, Massachusetts, United States of 
      America.
LA  - eng
GR  - DP2 AT009499/AT/NCCIH NIH HHS/United States
GR  - R01 AI130019/AI/NIAID NIH HHS/United States
GR  - R01 EY022054/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20210506
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
SB  - IM
MH  - Animals
MH  - *Disease Models, Animal
MH  - Female
MH  - Keratitis/etiology/metabolism/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neutrophils/*immunology
MH  - Nociceptors/*metabolism
MH  - Pseudomonas Infections/*complications
MH  - Pseudomonas aeruginosa/*physiology
MH  - Trigeminal Nerve Diseases/etiology/metabolism/*pathology
PMC - PMC8101935
COIS- No authors have competing interests.
EDAT- 2021/05/07 06:00
MHDA- 2021/10/05 06:00
PMCR- 2021/05/06
CRDT- 2021/05/06 18:06
PHST- 2020/09/08 00:00 [received]
PHST- 2021/04/13 00:00 [accepted]
PHST- 2021/05/06 18:06 [entrez]
PHST- 2021/05/07 06:00 [pubmed]
PHST- 2021/10/05 06:00 [medline]
PHST- 2021/05/06 00:00 [pmc-release]
AID - PPATHOGENS-D-20-01997 [pii]
AID - 10.1371/journal.ppat.1009557 [doi]
PST - epublish
SO  - PLoS Pathog. 2021 May 6;17(5):e1009557. doi: 10.1371/journal.ppat.1009557. 
      eCollection 2021 May.