Bibliographic record
Abstract
Introduction: Platelets are increasingly recognized for their roles in infection. Tuberculosis (TB) is characterized by excessive inflammation leading to disease and long-term sequelae. Platelets may be key drivers of immunopathology in TB, but the mechanisms involved are poorly understood. My hypothesis is that platelets regulate innate immune responses to TB. Methods: An in vitro model of M.tb-infected monocytes co-cultured with autologous platelets was interrogated using specific inhibitors and recombinant proteins. Gene expression of matrix metalloproteinases (MMPs) was assessed using quantitative PCR, and secretion using ELISA. Pulmonary TB patients, healthy controls, and patients undergoing diagnostic bronchoscopy were prospectively recruited. Agonist-induced platelet aggregation was quantified using light transmission aggregometry, and platelet activation and platelet-leukocyte binding measured using flow cytometry. Concentrations of cytokines, MMPs, and platelet-associated factors were assessed in bronchoalveolar lavage fluid (BALF) and plasma using Luminex multiplex analysis. Inflammatory responses were compared with those identified in a separate cohort of SARS-CoV-2-infected patients using multiplex analysis. Results: Platelets respond to M.tb-secreted antigens. Co-culture with platelets increases MMP gene expression and secretion by M.tb-stimulated monocytes. Platelets enhance M.tb-induced upregulation of monocyte phosphorylated phosphatidylinositol 3-kinase (PI3K) and mitogen activated protein kinase (MAPK) pathways through a combination of direct receptor-mediated and indirect secretory stimulation. Platelets from TB patients display a pro-inflammatory phenotype with decreased agonist-induced aggregation. Platelet-monocyte aggregation is increased in patients with TB and non-TB lung disease compared to healthy controls, but platelet-granulocyte aggregation was increased in TB patients only. Increased levels of inflammatory mediators including IP-10, platelet markers including von Willebrand factor (vWF), and MMPs were seen in both TB and SARS-CoV-2 infection; others including IL-8 showed divergent responses. Conclusions: This study presents cellular and clinical evidence that platelets adopt a TB-specific pro-inflammatory phenotype in pulmonary TB. This will inform the development of therapeutic agents aiming to limit harmful platelet-driven inflammation in TB.
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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 | 0.013 | 0.003 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.003 | 0.005 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.006 | 0.004 |
| Research integrity | 0.000 | 0.004 |
| 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 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".