Prolonged survival of E coli but not <i>Staphylococcus aureus</i> in monocytes from patients with Crohn's disease
Bibliographic record
Abstract
Introduction A primary macrophage defect has been proposed to play a role in Crohn's disease (CD) pathogenesis.1 In CD, Escherichia coli persist within lamina propria macrophages and peripheral blood monocytes are unable to effectively kill E coli in vitro.2 3 It is uncertain whether this abnormal bacterial handling by monocytes and macrophages in CD is limited to certain strains of E coli or whether a broader bacterial killing defect exists. The aim of this study was to compare intracellular survival of E coli with Staphylococcus aureus (not a usual resident of gut flora) within CD-derived and control monocytes. Methods Peripheral blood was taken from eight healthy controls and nine CD patients. CD distribution was ileal (n=1) and ileocolonic (n=8). Three CD patients were on thiopurines. Monocyte isolation was performed by iodixanol barrier flotation. Monocytes were challenged with a CD-derived strain of E coli and methicillin sensitive Staphylococcus aureus (MSSA). After 1 h incubation, the gentamicin protection assay was performed. Monocytes were lysed to release internalized bacteria after further incubation for 1 and 4 h. Cell lysates were plated on agar and incubated for 24 h at 37°C. Colony forming units (CFU) were counted after both 1 and 4h incubation. The CFU counts at these time points allowed relative replication to be determined. Results Viable CD-derived E coli were cultured from cell lysates at 1 and 4 h from 9/9 CD patients, and in 3/8 HC's (mean increase CFUs from 1 to 4 h: CD +394%, HC −7%). Viable S aureus was cultured in cell lysates at 1 and 4 h respectively from 1/9 and 0/9 CD patients and 0/8 healthy controls at both time points. The difference in the number of CFU's present for each subject at 1 and 4 h was calculated and there was a statistically significant difference in mean rank of (CFU (4 h) – CFU (1 h)) between CD and HC's for E coli but not for staph aureus (Mann–Whitney U test). Conclusion Within CD-derived peripheral monocytes, intracellular survival is prolonged for E coli but not for S aureus , illustrating that impairment of killing by monocytes in CD is restricted to particular bacteria. This is consistent with the clinical observation that CD primarily affects the gut which has an extensive but specific microbiome, rather than causing systemic immunodeficiency characterised by infections in other systems.
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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 | 0.000 | 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 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".