Neisseria gonorrhoeae infects the heterogeneous epithelia of the human cervix using distinct mechanisms
Bibliographic record
Abstract
Sexually transmitted infections are a critical public health issue.However, the mechanisms underlying sexually transmitted infections in women and the link between the infection mechanism and the wide range of clinical outcomes remain elusive due to a lack of research models mimicking human infection in vivo.We established a human cervical tissue explant model to mimic local Neisseria gonorrhoeae (GC) infections.We found that GC preferentially colonize the ectocervix by activating integrin-β1, which inhibits epithelial shedding.GC selectively penetrate into the squamocolumnar junction (TZ) and endocervical epithelia by inducing β-catenin phosphorylation, which leads to E-cadherin junction disassembly.Epithelial cells in various cervical regions differentially express carcinoembryonic antigenrelated cell adhesion molecules (CEACAMs), the host receptor for GC opacity-associated proteins (Opa CEA ).Relatively high levels were detected on the luminal membrane of ecto/ endocervical epithelial cells but very low levels intracellularly in TZ epithelial cells.CEA-CAM-Opa CEA interaction increased ecto/endocervical colonization and reduced endocervical penetration by increasing integrin-β1 activation and inhibiting β-catenin phosphorylation respectively, through CEACAM downstream signaling.Thus, the intrinsic properties of cervical epithelial cells and phase-variation of bacterial surface molecules both play a role in controlling GC infection mechanisms and infectivity, preferential colonization or penetration, potentially leading to asymptomatic or symptomatic infection. Author summaryGonorrhea, caused by Neisseria gonorrhoeae (GC), is a common sexually transmitted infection and has become a public health crisis due to a steady increase in antibiotic-resistant cases.How GC infect the female reproductive tract (FRT) and cause various clinical outcomes is still unknown.This study used human cervical explants to examine the mechanism by which GC infect the heterogeneous mucosa of the human cervix, the gate of the FRT.We show that GC preferentially colonize stratified epithelial cells in the vaginal-
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".