Neisseria gonorrhoeaePilus Attenuates Cytokine Response of Human Fallopian Tube Explants

Abstract

<jats:p><jats:italic>Background</jats:italic>. A role for pilus during attachment of<jats:italic>Neisseria gonorrhoeae</jats:italic>to epithelia of the female reproductive tract is currently assumed. However, Pil<jats:sup>−</jats:sup>gonococci have been observed during infection of the reproductive tract, which prompted us to examine the effect of pili on the dynamics of infection and the inflammatory responses of mucosal explants of the human Fallopian tube.<jats:italic>Methods</jats:italic>. Mucosal explants were infected in vitro with Opa negative Pil<jats:sup>−</jats:sup>and Pil<jats:sup>+</jats:sup><jats:italic>N. gonorrhoeae</jats:italic>strains.<jats:italic>Results</jats:italic>. Piliation enhanced gonococcal adherence to the epithelium within 3 h of infection (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:mrow></mml:math>) but thereafter did not offer advantage to gonococci to colonize the epithelial cell surface (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>P</mml:mi><mml:mo>&gt;</mml:mo><mml:mn>0.05</mml:mn></mml:mrow></mml:math>). No differences were found between the strains in numbers of gonococci inside epithelial cells. Pil<jats:sup>−</jats:sup>bacteria induced higher levels (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:mi>P</mml:mi><mml:mo>&lt;</mml:mo><mml:mn>0.05</mml:mn></mml:mrow></mml:math>) of IL-1β, TNF-α, GM-CSF, MCP-1, and MIP-1β than Pil<jats:sup>+</jats:sup>bacteria. There were no differences between both strains in LOS pattern, and Pil expression did not change after coincubation with mucosal strips.<jats:italic>Conclusions</jats:italic>. Results show that gonococcal invasion of the human Fallopian tube can occur independently of pilus or Opa expression, and suggest that pilus, by inhibition of several key elements of the initial inflammatory response, facilitates sustained infection of this organ.</jats:p>

Type IV Pilin Proteins: Versatile Molecular Modules

“…Neisseria causes cytoskeletal rearrangements that block bacterial uptake, a phenotype also caused by E. coli expressing bundle-forming pili (52), and induces membrane ruffling, enveloping adherent microcolonies and protecting them from shear forces (283). Neisseria also alters cell signaling and cytokine production (97,314,383,399) and impairs adherens and tight junction integrity, allowing bacteria to traverse polarized cell layers, including those forming the blood-brain barrier (110,111,248,334). Pilus retraction is a key facet of the Neisseria-host interaction, as infection with retractiondeficient mutants impairs cortical plaque formation and cytoprotective signaling (119), leading to higher levels of host cell apoptosis (179).…”

Peptidoglycan Fragment Release from Neisseria meningitidis

“…has been established to study the pathogenicity of the gonococcus (27). In this model, PG fragments from gonococci have been shown to cause ciliated cell death in fallopian tube mucosa (15) and infection with gonococci has been shown to induce the production of proinflammatory cytokines as well as cause ciliated cell death (28)(29)(30). Since PG fragments are known to stimulate the secretion of proinflammatory cytokines and chemokines, the human FTOC model could be used to evaluate the in vivo relevance of proportional differences in bacterial PG fragment release.…”

Treatment evaluation of Wharton’s jelly-derived mesenchymal stem cells using a chronic salpingitis model: an animal experiment

“…Additionally, TNF-α is closely associated with immunity of female genital organs [ 15 , 16 ]. When genital organs are infected or under inflammatory stimulation, high levels of TNF-α will aggravate the mucous epithelium of genital organs [ 17 , 18 ].…”