Regulatory T cells mediate the decreased susceptibility of males to Pseudomonas aeruginosa infection
Bibliographic record
Abstract
Abstract Background Sex hormones have been shown to play a role in the susceptibility of female patients with CF to P. aeruginosa chronic infection; however, the cellular mechanisms responsible for such sex-based imbalance are poorly understood. Accordingly, the aim of this study was to assess the role of the female sex hormone estrogen in a murine model of P. aeruginosa induced lung infection and to elucidate the cellular immune mechanisms involved. Methods The bacterial burden and inflammatory parameters following intranasal infections with P. aeruginosa were compared in male and female mice. Female mice were treated with anastrozole, which lowers estradiol, and the impact on survival assessed. Infection in male and female RAG1−/− mice, which lack T and B lymphocytes, and Foxp3DTR/GFP mice, in which Tregs can be selectively depleted, were also compared. Results We demonstrate that female adult mice are more susceptible to P. aeruginosa lung infection, compared to that of males, while this effect was not evident in pre-pubescent mice. Pre-treatment of female adult mice with anastrozole, resulted in increased survival and a greater ability to control P. aeruginosa induced lung infection, as evidenced by reduced bacterial burden in the lung and reduced levels of serum IL-6. This increased susceptibility of adult female mice to P. aeruginosa was not seen during infection in RAG1−/− mice, or following depletion of regulatory T cells (Tregs) in Foxp3DTR/GFP mice. In male mice, there was a significant increase in IL-6 levels following Treg depletion, demonstrating liberation from regulation, which did not occur in female mice. Conclusions This data demonstrates, for the first time, that the increased susceptibility of female mice to P. aeruginosa-induced lung infection is a result of the reduced action of Tregs. The potential benefits of targeting Treg activity in CF warrants further investigation in prevention and treatment of P. aeruginosa 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 | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.007 | 0.001 |
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".