<i>Citrobacter rodentium</i> Infection Induces MyD88-Dependent Formation of Ubiquitinated Protein Aggregates in the Intestinal Epithelium
Bibliographic record
Abstract
Citrobacter rodentium utilizes a type 3 secretion system (T3SS) to inject effector proteins into host intestinal epithelial cells, causing structural and functional changes in these cells during infection. Here, we examined the effects of C. rodentium infection on host cell protein ubiquitination in vivo. We observed the appearance of ubiquitinated protein (Ub(+)) aggregates in intestinal epithelial cells near the site of bacterial attachment. Formation of aggregates was dependent on T3SS activity and the effector translocated intimin receptor (Tir). Aggregates formed at 6 days after infection, when bacterial loads were maximal, but were absent at 12 days. Aggregates were not observed in MyD88(-/-) mice. Aggregate formation correlated with MyD88-dependent induction of NADPH oxidase 1, implicating reactive oxygen species in their formation. Aggregates were also observed in gastric tissues of mice infected with Helicobacter pylori. This is the first report describing the formation of Ub(+) aggregates in vivo during enteric infection, and reveals that this phenotype is dependent on both bacterial and host factors. Our experiments extend previous in vitro studies suggesting that Ub(+) aggregates play an important role in the initiation of immune responses to infection. Ub(+) aggregates are a novel marker of the cellular response to enteric pathogens and will be useful for studies of host-pathogen interactions in vivo.
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 | 0.001 |
| 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".