Unique properties of RV in an in vitro model of asthma exacerbation
Bibliographic record
Abstract
Background A vast majority of asthma exacerbations are linked to viral infections, most of which are caused by rhinovirus (RV). We hypothesize that eosinophils are key effector cells in asthma exacerbations. As such, using an in vitro model of human cells, we have shown that respiratory syncytial virus (RSV) and RV induce eosinophil degranulation when co-cultured with T-cells and autologous monocyte-derived dendritic cells (moDC), concurrent with moDC-dependent CD4+ CD45RO+ T-cell activation. While our original hypothesis has been that such activation is mediated solely by antigen-presentation (AP), our recent data also suggest that RV may be the major pathogen associated with asthma attacks because of its unique ability to interact directly with T-cells. Materials and methods Human monocytes, T-lymphocytes, autologous moDC and eosinophils (EOS) were isolated from blood. moDC were cultured with RSV, RV, or sham, then washed, and incubated with autologous T-cells. To determine the role for antigen presentation, some moDC were treated with the inhibitor chloroquine before virus culture. In some, no moDc were added and T lymphocytes (CD4, CD8 or a mix) were exposed to RSV, RV or UV-inactivated RV (RV-UV). T-cell activation and apoptosis were measured by flow cytometry (CD25 expression and Annexin-V/TO-PRO-3 staining, respectively), and proliferation by BrdU incorporation (Cell Proliferation ELISA, Roche). EOS cysteinyl-leukotriene (Cys-LT) release was measured by ELISA (Cayman Chemical). Cytokine release was measured by Searchlight (Pierce). Results RV presence induced a 5-fold increase in Cys-LT release from EOS co-cultured with T-cells and moDC, while RSV did not have any effect. In T-cell and moDC cocultures, RV induced greater increases in IL-1beta, IL10, IL-12p70, IL-13 and IFN-gamma compared with RSV. T-cells, and more evidently CD8+ T-cells, showed increased apoptosis when incubated with RV but not with RV-UV or RSV. Virus-loaded moDC induced proliferation of T-cells, but, unlike RSV, RV was insensitive to chloroquine. Conclusions Our results suggest that RSV and RV induce EOS and T-cell activation differentially. RSV induces proliferation in a MHC-II restricted antigen-presentation-dependent manner, while for RV this is not the sole pathway. In addition, based on cytokine and Cys-LT release, RV appears to be more potent compared to RSV. Our data are relevant to help understand why RV is so potent in the induction of asthma exacerbation in allergic patients, and will lead to novel potential targets for improved preventative strategies.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".