The Function of Phosphatidylinositol 3-Kinase delta (<u>PI3Kδ</u>) Enzyme in Protective Immunity to <i>Trypanosoma congolense</i> Infection in Mice: The Role of Regulatory B cells
Bibliographic record
Abstract
Abstract The delta isoform of PI 3-kinase (PI3Kδ) has important functions in B cell activation. Trypanosoma parasites utilize several mechanisms to exploit and evade host B cell and antibody responses critical for immunity. We sought to determine the impact of PI3Kδ in immunity to Trypanosoma congolense infection. We found that PI3KδD910A mutant mice show a surprisingly enhanced control of parasitemia in early infection (7–9 days) when compared to wild-type (WT) C57BL/6 mice. Drug treatment with Idelalisib to acutely inhibit PI3Kδ during infection in WT mice led to improved early control of parasitemia, consistent with results from genetically deficient mice. Both mutant mice and Idelalisib-treated mice showed a delay in polyclonal B cell activation and CD80/86 expression. Analysis of cytokine levels in the blood and peritoneal cavity showed higher IFNg and lower IL-10 levels in the drug-treated group at early time points, indicating a more pro-inflammatory environment. B1 cells were identified as the major IL-10 producing cells in the peritoneal cavity in early infection, and B1 cell production of IL-10 was significantly impaired by PI3Kδ-inhibitor treatment. We further observed increased Nitric oxide production in drug-treated mice, which correlated with increased parasite killing in early infection. Despite the improved early parasite control, there was a 100% mortality in PI3KδD910A mutants and 25% mortality in Idelalisib treated mice, presumably due to compromised generation of parasite-specific antibodies required to clear the first wave of blood infection. Our findings suggest that PI3Kδ inhibition impacts both regulatory B cell functions, affecting the early innate response, and generation of critical protective antibodies.
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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 | 0.001 |
| 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".