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.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".