A107 TOLL LIKE RECEPTOR 9 LIMITS INTESTINAL INFLAMMATION AND PROMOTES MICROBIOTA BASED COLONIZATION RESISTANCE DURING CITROBACTER RODENTIUM INFECTION
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Mammalian cells express a variety of toll-like receptors (TLRs) to detect and respond to microbial pathogens, such as enteropathogenic and enterohemorrhagic E. coli (EPEC and EHEC), two important human pathogens that are major causes of diarrheal diseases worldwide. Since EPEC and EHEC are human-specific, Citrobacter rodentium, a natural extracellular pathogen of mice has been widely used as a surrogate organism to study the role of immunity (including TLRs) in promoting host defense against EPEC and EHEC. These enteric pathogens share similar virulence strategies allowing them to directly infect the apical surface of the intestinal epithelium, resulting in host-driven intestinal inflammation. This study explored the potential role of TLR9, a receptor that recognizes unmethylated CpG dinucleotides present in bacterial DNA, in promoting host defense against C. rodentium infection. HEK293 cells co-transfected with the TLR9 and its reporter genes were treated with genomic DNA isolated from C. rodentium and the activity of the reporter was measured via a colorimetric assay. 8–12 week-old male and female wildtype (WT) C57BL/6J and TLR9 deficient (Tlr9-/-) mice were infected by oral gavage using 2 x 108 colony forming units (CFU) of streptomycin-resistant wildtype C. rodentium. Mice were monitored daily. An in vivo imaging system (IVIS) was used to visualize the colonization of C. rodentium in intact intestinal tissues. The mice were euthanized at day 6 post-infection and samples (cecum, colon and feces) were collected for further analysis such as CFU, histology, immunostaining, Western blot and quantitative PCR analysis. Tlr9-/-mice infected with C. rodentium suffered exaggerated mucosal damage and carried significantly higher intestinal pathogen burdens as compared to WT mice. C. rodentium infection also induced increased intestinal inflammatory and antimicrobial responses, as well as hyper-activation of NF-κB signaling in Tlr9-/-mice. These changes were associated with more rapid depletion of the intestinal microbiota in Tlr9-/-mice as compared to WT mice. Intriguingly, antibiotic based depletion of the gut microbiota in WT mice before C. rodentium infection increased their susceptibility to the levels seen in Tlr9-/- mice. Our results indicate that TLR9 suppresses intestinal inflammatory and antimicrobial responses during an enteric infection, thereby promoting microbiota-mediated colonization resistance against C. rodentium infection. CCC, CIHRNSERC, MITACs
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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 | 0.000 | 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) | 0.000 | 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