Disruption of type I interferon signaling causes sexually dimorphic dysregulation of anti-viral cytokines
Bibliographic record
Abstract
Type I interferons (IFNs) play a crucial role in the establishment of an antiviral state via signaling through their cognate type I IFN receptor (IFNAR). In this study, a replication-competent but highly attenuated strain of VSV (rVSVΔm51) carrying a deletion at position 51 of the matrix protein to remove suppression of anti-viral type I IFN responses was used to explore the effect of disrupted IFNAR signaling on inflammatory cytokine responses in mice. The kinetic responses of interleukin-6, tumor necrosis factor-α and interleukin-12 were evaluated in virus-infected male and female mice with or without concomitant antibody-mediated IFNAR-blockade. Unlike controls, both male and female IFNAR-blocked mice showed signs of sickness by 24-hours post-infection. Female IFNAR-blocked mice experienced greater morbidity as demonstrated by a significant decrease in body temperature. This was not the case for males. In addition, females with IFNAR-blockade mounted prolonged and exaggerated systemic inflammatory cytokine responses to rVSVΔm51. This was in stark contrast to controls with intact IFNAR signaling and males with IFNAR-blockade; they were able to down-regulate virus-induced inflammatory cytokine responses by 24-hours post-infection. Exaggerated cytokine responses in females with impaired IFNAR signaling was associated with more effective control of viremia than their male counterparts. However, the trade-off was greater immune-mediated morbidity. The results of this study demonstrated a role for IFNAR signaling in the down-regulation of antiviral cytokine responses, which was strongly influenced by sex. Our findings suggested that the potential to mount toxic cytokine responses to a virus with concomitant disruption of IFNAR signaling was heavily biased towards females.
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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) | 0.001 | 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 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".