Endocervical and Neutrophil Lipoxygenases Coordinate Neutrophil Transepithelial Migration to Neisseria gonorrhoeae.
J Infect Dis
; 218(10): 1663-1674, 2018 10 05.
Article
in En
| MEDLINE
| ID: mdl-29905822
ABSTRACT
Background:
Infection with Neisseria gonorrhoeae (GC) is characterized by robust neutrophil influx that is insufficient to clear the bacteria. Sustained neutrophilic inflammation contributes to serious clinical sequelae that particularly affect women, including pelvic inflammatory disease and infertility.Methods:
We established a 3-component system using GC, End1 polarized human endocervical cells, and primary human neutrophils to investigate neutrophil transepithelial migration following infection.Results:
Neutrophil migration across endocervical monolayers increased with the infectious dose and required GC-epithelial cell contact. Epithelial protein kinase C, cytosolic phospholipase A2, 12R-lipoxygenase (LOX), and eLOX3 hepoxilin synthase were required for neutrophil transmigration to GC, and migration was abrogated by blocking the MRP2 efflux pump and by adding recombinant soluble epoxide hydrolase. These results are all consistent with epithelial cell production of the neutrophil chemoattractant hepoxilin A3 (HXA3). Neutrophil transmigration was also accompanied by increasing apical concentrations of leukotriene B4 (LTB4). Neutrophil 5-lipoxygenase and active BLT1 receptor were required for apical LTB4 and neutrophil migration.Conclusions:
Our data support a model in which GC-endocervical cell contact infection stimulates HXA3 production, driving neutrophil migration that is amplified by neutrophil-derived LTB4. Therapeutic targeting of these pathways could limit inflammation and deleterious clinical sequelae in women with gonorrhea.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Host-Pathogen Interactions
/
Lipoxygenases
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Transendothelial and Transepithelial Migration
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Neisseria gonorrhoeae
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Neutrophils
Limits:
Female
/
Humans
Language:
En
Journal:
J Infect Dis
Year:
2018
Document type:
Article
Publication country:
EEUU
/
ESTADOS UNIDOS
/
ESTADOS UNIDOS DA AMERICA
/
EUA
/
UNITED STATES
/
UNITED STATES OF AMERICA
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US
/
USA