The Mucin Muc2 Limits Pathogen Burdens and Epithelial Barrier Dysfunction during Salmonella enterica Serovar Typhimurium Colitis
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Bibliographic record
Abstract
Salmonella enterica serovar Typhimurium is a model organism used to explore the virulence strategies underlying Salmonella pathogenesis. Although intestinal mucus is the first line of defense in the intestine, its role in protection against Salmonella is still unclear. The intestinal mucus layer is composed primarily of the Muc2 mucin, a heavily O-glycosylated glycoprotein. The core 3-derived O-glycans of Muc2 are synthesized by core 3 β1,3-N-acetylglucosaminyltransferase (C3GnT). Mice lacking these glycans still produce Muc2 but display a thinner intestinal mucus barrier. We began our investigations by comparing Salmonella-induced colitis and mucus dynamics in Muc2-deficient (Muc2(-/-)) mice, C3GnT(-/-) mice, and wild-type C57BL/6 (WT) mice. Salmonella infection led to increases in luminal Muc2 secretion in WT and C3GnT(-/-) mice. When Muc2(-/-) mice were infected with Salmonella, they showed dramatic susceptibility to infection, carrying significantly higher cecal and liver pathogen burdens, and developing significantly higher barrier disruption and higher mortality rates, than WT mice. We found that the exaggerated barrier disruption in infected Muc2(-/-) mice was invA dependent. We also tested the susceptibility of C3GnT(-/-) mice and found that they carried pathogen burdens similar to those of WT mice but developed exaggerated barrier disruption. Moreover, we found that Muc2(-/-) mice were impaired in intestinal alkaline phosphatase (IAP) expression and lipopolysaccharide (LPS) detoxification activity in their ceca, potentially explaining their high mortality rates during infection. Our data suggest that the intestinal mucus layer (Muc2) and core 3 O-glycosylation play critical roles in controlling Salmonella intestinal burdens and intestinal epithelial barrier function, respectively.
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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 | 0.001 | 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 it