O10.5 Repeated, low dose Chlamydia infections trigger aberrant immune responses and enhanced tissue pathology
Bibliographic record
Abstract
Introduction Chlamydia trachomatis (Ct) infections severely impact women’s health due to pelvic inflammatory disease (PID), and, for unclear reasons, repeated infections are correlated with severity. Contributions from animal studies, using a single inoculation, have imparted valuable findings, but utilizing a repeated infection model could expand the understanding of Ct driven tissue damage. We hypothesize that, compared to single infections, repeated Chlamydia infection dysregulates the immune response, and results in more severe pathology. Methods We inoculated mice with C. muridarum (Cm) using the conventional, single dose (1 dose of 6*10^5 IFU; 1X), or repeated, low dose infections with the same cumulative number of bacteria (5 doses of 1.2*10^5 IFU; 5X), and assessed the cellular, molecular, and pathology indicators of their immune response on days 10, 23, and 30 post-initial infection. Results Following 5X infection, pathology severity, indicated by oviduct cyst diameter, was significantly increased compared to the 1X group. This increase was associated with significantly elevated neutrophilic influx and pro-inflammatory cyto/chemokine concentrations in the genital tracts of 5X, but not 1X, infected animals, denoting differential host responses. IgG1 levels were markedly higher in the 5X group, while IgG2a levels were significantly higher in the 1X group, suggesting a skewed Th2 response in the 5X group, indicating a potential mechanism of pathology development following repeated infections. Variances in bacterial burden did not account for these differences, as both groups had similar levels of bacterial shedding. Conclusions Repeated Cm exposure induces a distinct molecular response, triggering maladaptive neutrophil recruitment, leading to a pathogenic modulation of T helper responses that promote tissue damage. These findings demonstrate the potential of repeated infection models to provide insight into the immune and pathology states in humans, and may be of value in elucidating, and targeting interventions to, host mediators of tissue damage during Ct infection.
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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) | 0.000 | 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 | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".