Mitochondrial Cyclophilin D is a critical regulator of T cell mediated immunity to «Mycobacterium tuberculosis»
Bibliographic record
Abstract
Despite the world-wide application of BCG vaccination and other anti-Mycobacterium tuberculosis (Mtb) interventions, Mtb remains one of the most pervasive human pathogens.The ability of Mtb to persist in individuals with apparently normal immune systems implies that Mtb has developed strategies to evade and even subvert innate and adaptive immunity.The high success of this pathogen is closely linked to its ability to alter the intracellular environment of the alveolar macrophages (Mφ).Mtb eventually induces necrosis, a type of cell death that favors Mtb survival and progression of disease.Interestingly, virulent Mtb actively inhibit apoptosis, an alternate form of Mφ death, which is beneficial to the host, allowing for elimination of intracellular bacilli and instruction of adaptive immune responses.Cyclophillin D (CypD) is a mitochondrial matrix protein that has recently been implicated in regulating necrotic but not the apoptotic cell death program.Since CypD is essential for the induction of necrosis, which is also an exit mechanism for Mtb, we hypothesize that the lossof-function in CypD enhances immunity to tuberculosis.To investigate the potential protective effect of CypD deficiency against tuberculosis infection, wild-type C57BL/6 and CypD-deficient mice were aerosolized with H37Rv (~100 CFU).After 14, 35, and 90 days of infection, the lung bacterial burden was similar between CypD -/-and wild-type mice.Surprisingly, CypD -/-mice were highly susceptible to infection with significantly increased mortality.The frequency and total cell numbers of CD4+, CD8+ T cells, as well as antigen specific CD8+ T cell response (H-2K b -TB10.44-11 ), were significantly increased in the lungs of Mtb infected CypD -/-mice.This uncontrolled T cell mediated immune response was correlated with enhanced immunopathology.Subsequent analyses of CypD-deficient 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".