Inflammasome adaptor protein ASC is critical for the immune response and survival in West Nile virus encephalitis (P6110)
Bibliographic record
Abstract
Abstract Innate immune responses are essential for WNV clearance, dissemination and neurovirulence. Pattern recognition receptors and other danger signals activate assembly of inflammasome complex, which modulates antiviral defense responses. ASC is an important adaptor molecule, which mediates downstream signaling pathways of NLRP3 inflammasomes. In this study we defined the role of ASC in WNV immunity. Infection of cultured BMDCs showed that ASC was essential for the activation of caspase-1, a key component of inflammasome assembly. ASC-/- mice were highly susceptible to WNV infection marked by increased mortality, enhanced viremia and virus replication in the CNS. As compared to wild type mice, key cytokines including IL-1β and IFN-γ were significantly reduced in the sera of ASC mice. Additionally, antiviral IFN-α levels were also decreased in the sera of ASC-/- mice. Increased virus titers in the brain of ASC-/- mice correlated with increased inflammation and neuronal apoptosis. However, intracranial inoculation of WNV did not result in significant differences in the virus titers in both groups suggesting that impaired immune response coupled with failure to clear virus in the periphery leads to increased neuropathology and mortality in ASC-/- mice. Collectively, our data provides new insights into the role of ASC as an essential modulator of inflammasome-dependent and -independent immune response to effectively control WNV infection.
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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) | 0.002 | 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".