Requirement of TLR2-mediated signaling for the induction of IL-15 gene expression in human monocytic cells by HSV-1
Bibliographic record
Abstract
Exposure of human monocytic cells to herpes simplex virus type 1 (HSV-1) results in immediate up-regulation of interleukin (IL)-15 gene expression. However, the receptor involved in this induction is not known. Here, we provide evidence that this induction depends on TLR2-mediated signaling pathway. Through the use of small interfering RNAs (siRNAs), we demonstrate that HSV-1-induced up-regulation of IL-15 gene expression in monocytic THP1 cells requires the presence of the adaptors MyD88, IRAK1, and TRAF6. Interestingly, TIRAP/Mal, an adaptor molecule specifically recruited to TLR2 and TLR4, was also required for maximal up-regulation of IL-15. This response was completely abrogated by anti-TLR2, but not anti-TLR4, blocking mAbs in both primary monocytes and THP1 cells. Furthermore, THP1 cells rendered defective in TLR2 expression by disrupting the expression of Sp1, a major transcription factor involved in TLR2 promoter activity, were unable to up-regulate IL-15 gene expression in response to HSV-1. In addition, HSV-1-induced NF-kappaB activation was significantly reduced after neutralization of TLR2 and the adaptor proteins. Altogether, these results unequivocally show that HSV-1 induces TLR2-dependent activation of IL-15 gene expression, which requires the recruitment of both MyD88 and TIRAP/Mal and the activation of IRAK1 and TRAF6 leading to NF-kappaB translocation to the nucleus.
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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 | 0.000 | 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) | 0.000 | 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".