Mycobacterium tuberculosis manipulates LINC02528 in macrophages to modulate anti-tuberculosis metabolic immunity
Bibliographic record
Abstract
Host defenses are crucial in deciding the fate of Mycobacterium tuberculosis (Mtb) infections, as less than 10% of infected individuals develop tuberculosis. Oxidative stress plays a critical role in the host defense against Mtb. However, the mechanisms by which Mtb modulates redox homeostasis to evade immune responses remain poorly understood. In this study, we primarily identified a pathogen-responsive long noncoding RNA, LINC02528, which was selectively upregulated in peripheral blood mononuclear cells (PBMCs) from tuberculosis (TB) patients. In Mtb-infected macrophages, LINC02528 dynamically relocalizes from the nucleus to the cytoplasm. Functionally, CRISPR-Cas9-mediated knockout (KO) of LINC02528 in macrophages resulted in reduced Mtb survival concurrent with an elevated IL-1β expression. Importantly, these antimicrobial effects were abrogated by IL-1 receptor antagonist (IL-RA) treatment. Interestingly, LINC02528 was found to directly bind to TOMM22, a mitochondrial outer membrane translocase, as validated by co-localization analysis using in situ hybridization of lung tissue sections from a TB patient. The ECAR results revealed that LINC02528 deficiency significantly increased glycolysis and elevated Mtb-induced mitochondrial ROS (mtROS) production. Notably, TOMM22 knockdown phenocopied LINC02528 deletion effects, suggesting functional interdependence in modulating mitochondrial dynamics and the host's anti-TB immunity. Collectively, our findings reveal a novel strategy wherein Mtb hijacks the lncRNA-mitochondrial axis to rewire redox-metabolic checkpoints to favor immune evasion. Targeting LINC02528 could dually disrupt the pathogen-permissive redox balance and activate mtROS-IL-1β-mediated antimicrobial defense, offering novel therapeutic avenues for TB.
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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 | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| 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) | 0.000 | 0.001 |
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".