A25 INVESTIGATING THE ROLE OF TOLL-INTERACTING PROTEIN DURING <i>CITROBACTER RODENTIUM</i> INFECTION
Bibliographic record
Abstract
Abstract Background Diarrheal diseases are a threat to human health, being the second leading cause of death in children. Diarrheic enterocolitis can be caused by attaching/effacing (A/E) pathogens like enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC). Citrobacter rodentium (CR), a mouse A/E pathogen, mimics EPEC and EHEC infections, causing goblet cell depletion, crypt hyperplasia, and leukocyte infiltration. Autophagy, a critical immune pathway linked to goblet cell mucus secretion, is involved in the defence against CR. Toll-interacting protein (Tollip) is an intracellular mediator of autophagy and immunity, but its role in A/E infections remains elusive. This study aims to test the hypothesis that Tollip plays a protective role in CR infection. Aims - Assess CR infection kinetics in WT and Tollip-/- mice. - Assess colitis in CR-infected WT and Tollip-/- mice. Methods Bacterial load was assessed by fecal colony forming unit (CFU) count in CR-infected WT and Tollip-/- mice. Histological damage was evaluated by scoring epithelial damage, leukocyte infiltration and crypt hyperplasia in H&E-stained distal colon sections. Apoptotic cells were identified by TUNEL. Acid and neutral mucin production was evaluated by Alcian-PAS staining. Glycosylation patterns were determined by immunofluorescence with lectins specific to sialic acid- and fucose-bound mucins. Results Tollip -/- and WT mice showed similar infection kinetics during the establishment and expansion phases (2-6 days post-infection (dpi)) and steady-state (7-14 dpi), with a peak of bacterial counts at 10 dpi. WT mice cleared CR by day 15, but Tollip-/- still shed bacteria by 17 dpi. The colitis grade was similar between WT and Tollip-/- mice, with marked epithelial damage at 8 dpi and increased leukocyte infiltration at 17 dpi. Scarce apoptotic cells (<4 per field) were detected in WT and Tollip-/- mice during infection. Tollip-/- showed a thinner colonic mucin barrier and less mucin-filled goblet cells at 17 dpi compared to WT mice. CR-infected Tollip-/- mice showed altered mucin glycosylation patterns, with lower fucosylated mucins in the upper crypt and lumen and increased sialic acid-bound mucins in the luminal barrier and lower crypt. The mucin barrier, goblet cells, and mucin glycosylation were similar in uninfected Tollip-/- and WT mice. Conclusions This study demonstrates a new protective role for Tollip, particularly during the resolution phase, as a lack of Tollip delayed the clearance of CR. This phenotype could be explained by deficiencies in the mucin layer observed in Tollip-/- mice, evidenced by lower mucin production and anomalies in mucin glycosylation. By enhancing our understanding of host-pathogen interactions during enteric infections, this research serves as a step in the development of new treatments and prevention strategies. Funding Agencies None
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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 | 0.001 | 0.001 |
| 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".