Schistosome Soluble Egg Antigen Decreases<i>Mycobacterium tuberculosis</i>–Specific CD4<sup>+</sup>T-Cell Effector Function With Concomitant Arrest of Macrophage Phago-Lysosome Maturation
Bibliographic record
Abstract
Helminth-infected individuals possess a higher risk of developing tuberculosis, but the precise immunologic mechanism of Mycobacterium tuberculosis control remains unclear. We hypothesized that a perturbation of the M. tuberculosis-specific CD4(+) T-cell response weakens the ability of macrophages to contain M. tuberculosis We exposed peripheral blood mononuclear cells from M. tuberculosis-infected humans to schistosome soluble egg antigen (SEA) and then profiled M. tuberculosis-specific CD4(+) T cells via multiparametric flow cytometry. SEA decreased the frequency of cells producing interferon γ (6.79% vs 3.20%; P = .017) and tumor necrosis factor α (6.98% vs 2.96%; P = .012), with a concomitant increase in the median fluorescence intensity of interleukin 4 (IL-4; P < .05) and interleukin 10 (IL-10; 1440 vs 1273; P < .05). Macrophages polarized with SEA-exposed, autologous CD4(+) T-cell supernatant had a 2.19-fold decreased colocalization of lysosomes and M. tuberculosis (P < .05). When polarized with IL-4 or IL-10, macrophages had increased expression of CD206 (P < .0001), 1.5-fold and 1.9 fold increased intracellular numbers of M. tuberculosis per macrophage (P < .0005), and 1.4-fold and 1.7-fold decreased colocalization between M. tuberculosis and lysosomes (P < .001). This clarifies a relationship in which helminth-induced CD4(+) T cells disrupt M. tuberculosis control by macrophages, thereby providing a mechanism for the observation that helminth infection advances the progression of tuberculosis among patients with M. tuberculosis infection.
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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 | 0.000 |
| 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 | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".