Calpain proteases are required for effective clearance of enterobacteria within the peritoneum of mice to prevent systemic infection (112.5)
Bibliographic record
Abstract
Abstract The ubiquitously expressed calpain 1 and 2 isoforms are heterodimers consisting of a catalytic subunit (capn1 or capn2), and a common regulatory capns1-encoded subunit, which is required for protease stability and activity. Although calpains regulate neutrophil and macrophage activation, their roles in immunity remain poorly defined. Here, we use fes-driven Cre recombinase (fes-Cre) to delete capns1 in mice, thus eliminating calpain 1/2 activity in Cre-expressing cells. We detect near complete capns1 deletion in hematopoietic cells, consistent with the tissue-specific expression pattern of fes. Next, we compared the response of control and capns1 targeted mice in the feces-in-peritoneum (FIP) model of sepsis (i.p. injection of enterobacteria). At 2-6 hours post infection, mice were sacrificed and bacterial load, neutrophil recruitment, and cytokine levels in peritoneal lavage fluid (PLF) and peripheral blood were compared between genotypes. We observed comparable levels of neutrophil infiltration and cytokine production in PLF from control and capns1 targeted FIP-treated mice. However, bacterial killing was highly reduced (>10-fold) in capns1 targeted compared to control mice; and this correlated with increased enterobacterial escape to the peripheral blood. These observations suggest that calpains are not required for inflammatory cytokine production or neutrophil recruitment, but they are required for bacterial clearance, and may protection against development of sepsis.
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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) | 0.001 | 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 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".