A129 THE ROLE OF BACTERIAL HTPG IN HOST-MICROBIOME INTERACTIONS IN CROHN’S DISEASE
Bibliographic record
Abstract
The bacterial chaperone high temperature protein G (HtpG), a homolog of eukaryotic heat shock protein 90 (Hsp90), functions to protect bacteria by stabilizing proteins against a variety of environmental stresses. We recently observed increased abundance of HtpG amongst several metagenomic pathways associated with sustained remission in pediatric Crohn’s disease patients treated with exclusive enteral nutrition (Dunn et al., 2016). HtpG and other chaperones from several bacteria have been reported to induce the production of CXCL8 in human fibroblasts, endothelial cells, and monocytes (Shelburne et al., 2007). Bacterial heat shock proteins (e.g. Hsp65) have been reported to protect against colitis in mice (Gomes-Santos et al., 2017). Understanding the impact of bacterial HtpG on intestinal immune responses will provide important mechanistic insight into how HtpG may promote sustained remission following exclusive enteral nutrition. To establish the degree of impact that HtpG has on innate immune functions of intestinal epithelial cells. HT-29 cells (a human colon adenocarcinoma cell line) were treated with Bacteroides fragilis recombinant (r) HtpG (2 μg/ml or 10 μg/ml), or media alone for 24 hours. CXCL8 cytokine expression was measured from HT-29 supernatants using an ELISA assay. Preliminary data indicate that lower concentrations of rHtpG result in increased CXCL8 cytokine expression in HT-29 cells. In comparison to the media control, CXCL8 expression in cells treated with 2 μg/ml rHtpG was markedly increased and greater than cells treated with 10 μg/ml rHtpG. We found that lower concentrations of bacterial HtpG, as observed in pediatric Crohn’s disease patients unable to sustain remission, resulted in increased expression of CXCL8 in intestinal epithelial cells. These findings may be of particular relevance to the subset of Crohn’s disease patients who have an innate immune dysfunction associated with lower neutrophil chemotaxis (Marks et al., 2006). CIHR
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How this classification was reachedexpand
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 | 0.002 | 0.001 |
| 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 | 0.001 | 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 teacher head, 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".