The PD-1/PD-L costimulatory pathway plays a key role in Histoplasma capsulatum pathogenesis (B122)
Bibliographic record
Abstract
Abstract The PD-1 costimulatory receptor negatively regulates T cell receptor signaling upon interacting with its ligands PDL1 and PDL2 expressed on antigen presenting cells (APCs) and has a key role in maintaining self-tolerance. In the present study we examined the role of PD-1 in Histoplasma capsulatum (Hc) infection. Hc is a human pathogenic dimorphic fungus that replicates within macrophages in vivo. To characterize immune responses in murine histoplasmosis, macrophages, as well as splenocytes were analyzed after intranasal infection with Hc. qRT-PCR and FACS analysis showed significant, IFN-γ-mediated up-regulation of PDL1 on both macrophages and splenocytes. The role of the PD-1 pathway in Hc pathogenesis is further demonstrated by the significant (100%) survival of PD-1 deficient mice infected with a lethal dose of Hc. Although initially inflammatory reactions developed in the lungs, the mice were disease free by day 10, as shown by histological analysis and cfu values. Also, when Hc infected C57BL/6 mice were treated with blocking anti-PD-1 monoclonal antibody, there was a significant increase in the survival of the animals (70%), whereas all untreated mice died. Our results show for the first time the importance of the PD-1/PDL pathway in anti-fungal immunity, and offer novel strategies for immunotherapy in clinical histoplasmosis.
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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".