Bibliographic record
Abstract
The bacterial species Neisseria gonorrhoeae remains one of the most prevalent bacterial causes of sexually transmitted infections. Gonorrhea is typically characterized by a painful purulent discharge and inflammation, the outcome of overzealous recruitment of neutrophils, phagocytic immune cells highly specialized in the detection and elimination of microbial pathogens. Although molecular mechanisms of gonococcal pathogenesis have been studied in great detail, the causes for the excessive inflammation and immunopathology that follow infection are still not clear. The human neutrophil-restricted innate immune receptor CEACAM3 has been previously shown to promote opsonin-independent uptake and killing of N. gonorrhoeae by neutrophils. In the course of my thesis work, I have established that the role of CEACAM3 is not restricted to the neutrophils’ direct engulfment and killing of gonococci, since it also drives a vigorous inflammatory response that typifies gonorrhea. By carrying the potential to mobilize increasing numbers of neutrophils, CEACAM3 represents a tipping point between the protective and pathogenic outcomes of N. gonorrhoeae infection. My biochemical profiling of gonococcal-infected, genetically modified neutrophils revealed that CEACAM3 engagement triggers a Syk-, PKCδ-, Bcl10-MALT1-, and Tak1-dependent signaling cascade that leads to the activation of an NF-κB-dependent transcriptional response, with consequent production of pro-inflammatory cytokines. I also showed that CEACAM cross-linking on neutrophils signals in synergy with TLR4, significantly amplifying the response to LPS, suggesting that CEACAM3 acts as an integral part of a complex innate immune detection network. Finally, I co-led a study that characterized Opa protein variant expression among a collection of clinical specimen-derived N. gonorrhoeae, and then assessed their CEACAM binding profile. This study suggested that mucosal infection in humans selects for binding to epithelial-expressed CEACAMs but against CEACAM3 binding in vivo. Together, my studies implicate a role for CEACAM3 as a host-adaptive innate receptor that promotes gonococcal detection and elimination in the context of natural infection, but also reveal potential pathogenic consequences of CEACAM3 activation.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".