«Citrobacter rodentium» causes fatal diarrhea through R-spondin 2-mediated activation of Wnt signaling
Bibliographic record
Abstract
Acute infectious diarrhea is a serious cause of morbidity and mortality worldwide, in particular among young children in the developing world.Citrobacter rodentium is a mouse-specific pathogen that is widely used as a model for the human-specific diarrheal pathogens enteropathogenic and enterohemorrhagic Escherichia coli (EPEC and EHEC).Despite evidence of variability in disease severity and outcome of EPEC and EHEC infection, little is known about the mechanisms that regulate host susceptibility to these organisms.However, the inter-strain differences in susceptibility of mice to C. rodentium can be used to identify genes involved in host response to infection.To this end, we recently identified a major genetic locus within the mouse genome on chromosome 15 that controls mortality during C. rodentium infection.In order to characterize the genetic control of susceptibility to C. rodentium, we first refined the boundaries of the locus of interest using subcongenic mice, which defined a region of 4 Mb containing eight annotated genes.We examined mRNA expression of these genes in colonic tissue in response to infection.Of these genes, R-spondin 2 (Rspo2), an activator of the Wnt/βcatenin signaling pathway, was found to be upregulated by as much as 80-fold in colonic tissue in susceptible mice in response to infection with C. rodentium.We confirmed Rspo2 induction in several other susceptible mouse strains.Rspo2 is an activator of the βcatenin signaling cascade through the canonical Wnt pathway.Thus, we propose that Rspo2 induction in susceptible mice drives a potent Wnt-mediated proliferative response of colonic crypt cells, leading to immature and poorly differentiated colonic epithelium.This work highlights a novel mechanism of susceptibility to bacterium-induced diarrheal disease, and suggests new targets for the treatment of infectious diarrhea.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.000 | 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 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".