Impairment of dendritic cell function by excretory‐secretory products: A potential mechanism for nematode‐induced immunosuppression
Bibliographic record
Abstract
To determine whether helminth-derived products modulate dendritic cell (DC) function, we investigated the effects of excretory-secretory products (ES) and adult worm homogenate (AWH) derived from the gastrointestinal nematode Heligmosomoides polygyrus (Hp) on murine bone marrow-derived DC (BMDC). Compared to the TLR9 ligand CpG, Hp-derived products alone failed to induce DC activation. ES, but not AWH, inhibited BMDC cytokine and chemokine production and co-stimulatory molecule expression (CD40, CD86 and MHC class II) induced by TLR ligation. TLR ligand-independent, PMA-induced DC activation was unaffected by ES. Recipients of ES-treated BMDC pulsed with OVA had suppressed Ab responses in vivo, irrespective of the Th1 or Th2 isotype affiliation, compared to recipients of control OVA-pulsed BMDC. Importantly, suppression occurred even in the presence of the potent type 1 adjuvant CpG. In contrast to untreated OVA-pulsed BMDC, ES-treated BMDC pulsed with OVA had reduced co-stimulatory molecule and cytokine expression. CD4(+)CD25(+)Foxp3(-) T cells, which secreted high IL-10 levels, were generated in co-cultures of OT-II OVA-specific TCR-transgenic CD4(+) T cells and ES-treated BMDC. These IL-10-secreting T cells suppressed effector CD4(+) T cell proliferation and IFN-gamma production, the latter effect mediated by an IL-10-dependent mechanism. Together, these results demonstrate that nematode ES impaired DC function and suppressed both Th1 and Th2 adaptive immune responses possibly by inducing regulatory T cells.
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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 | 0.000 | 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 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".