Bibliographic record
Abstract
Problem: There is growing interest in the role of viral infections and their association with adverse pregnancy outcomes.While the trophoblast is permissive to viruses, little is known about their impact on the placenta.We previously established that the Toll-like receptor 8 (TLR8) agonist, viral ssRNA, induces a pro-inflammatory cytokine response in first trimester trophoblast.Thus, we sought to determine the mechanisms involved, and whether viral ssRNA could induce an antiviral response.Methods of study: The human first trimester trophoblast cell line, HTR8, was stably transfected to express either a TLR8 dominant negative (DN) or MyD88-DN.The wildtype, TLR8-DN or MyD88-DN cells were treated with or without viral ssRNA (5 µg/mL).After 12 hr, RNA was extracted and qRT-PCR performed for pro-inflammatory cytokines [IL-8, IL-6]; type I interferons [IFNa, IFNb], antiviral factors [2 0 ,5 0 -oligoadenylate synthetase (OAS), Myxovirus-resistance A (MxA) and apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G)]; and antimicrobial peptides [secretory leukocyte protease inhibitor (SLPI), human beta defensin-1 (HBD1) and HBD2].Results: Treatment of wildtype trophoblast with ssRNA significantly increased mRNA for IL-6 by 8.3fold; IL-8 by 1.3-fold; IFNa by 2.6-fold; IFNb by 3.6fold; OAS by 1.4-fold; MxA by 2.5-fold; APOBEC3G by 2.2-fold; and SLPI by 2.3-fold, compared to untreated controls (P < 0.05).ssRNA had no effect on HBD1/2 expression.The TLR8-DN significantly inhibited ssRNA-induced IL-6 by 70.1%; IL-8 by 61.7%; IFNa by 48.1%; and SLPI by 58.6%, compared to wildtype cells (P < 0.05).Similarly, the MyD88-DN significantly inhibited ssRNA-induced IL-6 by 69.4%; IL-8 by 70%; IFNa by 64.6%; and SLPI by 55.4%.Viral ssRNA-induced upregulation of IFNb, OAS, MxA and APOBEC3G was unaffected by either the TLR8-DN or MyD88-DN.Conclusions: These findings demonstrate that viral ssRNA induces a trophoblast inflammatory cytokine, IFNa, and SLPI response through TLR8 and MyD88.In contrast, the ssRNA-induced IFNb and subsequent antiviral response occurs independently of the TLR8/ MyD88 pathway.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".