Adult asthmatics display exaggerated IFNγ responses to human metapneumovirus and respiratory syncytial virusThis paper is one of a selection of papers in this Special Issue, entitled International Symposium on Recent Advances in Molecular, Clinical, and Social Medicine, and has undergone the Journal's usual peer-review process.
Bibliographic record
Abstract
Human metapneumovirus and respiratory syncytial virus are RNA viruses associated with lower respiratory tract infections. Regular symptomatic re-infection and sequelae are common, particularly in individuals with pre-existing respiratory diseases, such as asthma. Our understanding of virus-dependent cytokine responses and potential differences between allergic asthmatics and non-asthmatics is limited. To test our hypothesis that adults with mild allergic asthma, the most common form of this disease, exhibit distinct pro-inflammatory responses, we developed a model using acute in vitro infection of fresh peripheral blood mononuclear cells. For both viruses, the production of innate-immunity-associated IL-6 and IL-10 was indistinguishable in the 2 populations. Type 1 cytokine production dominated adaptive immune responses in both asthmatic and non-asthmatic individuals. Surprisingly, asthmatics exhibited stronger pro-inflammatory IFNgamma production in response to human metapneumovirus than non-asthmatic adults (p = 0.01), with a similar, but statistically nonsignificant trend in the respiratory-syncytial-virus-stimulated response. Neutralizing IL-10 did not enhance the intensity of IFNgamma responses, demonstrating that this pro-inflammatory bias is not counter-regulated by IL-10. Finally, anti-TLR4 blocked lipopolysaccharide, but not respiratory-syncytial-virus-driven cytokine production. Collectively, the data demonstrate that asthma is characterized by markedly stronger pro-inflammatory IFNgamma responses to pneumoviruses than their non-asthmatic counterparts. This distinctive pattern of viral immunity may contribute to a worsening of asthma symptoms during respiratory virus infections.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".