1187. CFTR Function Impacts Proinflammatory Cytokine Expression of Bronchial Epithelial Cells During <i>Pseudomonas aeruginosa</i> and <i>Staphylococcus aureus</i> Infections
Bibliographic record
Abstract
Abstract Background Cystic fibrosis (CF) is a genetic disease in which opportunistic respiratory infections are common, particularly with P. aeruginosa and S. aureus. It has been suggested that dysfunction in the cystic fibrosis transmembrane conductance regulator (CFTR) could impact host immune response to these infections. The aim of this study was to determine if dysfunction in the CFTR gene could impact host cell death and the expression of proinflammatory cytokines. Methods We used two human bronchial epithelial (HBE) cell lines NuLi-1 and CuFi-1, which were recovered from individuals without and with CF, respectively. THP-1 cells were also differentiated into a macrophage phenotype with 50ng/mL PMA, and 10 µM CFTRinh-172 was used to impair CFTR function in these cells. Laboratory reference strains PAO1 and S. aureus 6538 were used to conduct in vitro infections. Host cell death at various MOIs was evaluated using a neutral red uptake assay, and cytokine expression was measured using ELISAs. Results No differences in THP-1 cell death or cytokine expression were observed for infections with S. aureus 6538 or PAO1 with and without CFTRinh-172. No differences in cell death for infections with the HBE cells and either bacteria were noted. S. aureus 6538 induced higher levels of IL-1β when infecting CuFi-1 cells in comparison to NuLi-1 cells across all MOIs (P &lt; 0.001) and induced higher levels of IL-6 at an MOI of 100 (P &lt; 0.01). S. aureus 6538 also induced higher levels of IL-8 when infecting CuFi-1 cells in comparison to NuLi-1 at MOIs of 1 and 10 (P &lt; 0.05 and P &lt; 0.01, respectively). Meanwhile, PAO1 induced less IL-6 expression when infecting CuFI-1 cells at an MOI of 1 and 10 (P &lt; 0.01 and P &lt; 0.01, respectively). CuFi-1 cells infected with PAO1 had less IL-8 expression in comparison to infected NuLi-1 cells for all MOIs (P &lt; 0.01), but no differences in IL-1β expression were observed when infecting either cell line with PAO1. Conclusion Bronchial epithelial cells with and without functional CFTR appear to respond differently to infections with either P. aeruginosa or S. aureus. Further elucidating how various immune response pathways are impacted by CFTR dysfunction may lead to alternative approaches to therapy to reduce morbidity observed among CF patients. Disclosures All Authors: No reported disclosures
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.001 |
| 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".