MicroRNA-mediated regulatory mechanisms in cow’s ileum and ileum lymph node in response to Mycobacterium avium subspecies paratuberculosis infection
Bibliographic record
Abstract
Mycobacterium avium subsp. paratuberculosis (MAP) causes Johne’s disease (JD), a chronic enteritis infection affecting ruminants with significant economic implications for the dairy industry. The molecular regulatory mechanisms governing host responses to MAP infection remain unclear. This study elucidated the roles of microRNAs (miRNAs) in the ileum (IL), ileal lymph node (ILLN), and liver of cows during subclinical MAP infection. Tissues (IL, ILLN, and liver) were collected from four JD-positive (JDP), five MAP-tolerant (MAPT), and five healthy control (HC) cows. MiRNA transcriptomes were analyzed using miRNA-sequencing, differential miRNA expression, correlation, and functional analyses. A total of 441, 405, and 201 miRNAs were identified in IL, ILLN, and liver, respectively, including 12 miRNAs highly expressed across all three tissues. ILLN exhibited more differentially expressed (DE) miRNAs, including 20 (JDP vs. HC), 21 (MAPT vs. HC), and 15 (JDP vs. MAPT) than the IL: 17 (JDP vs. HC), 8 (MAPT vs. HC), and 6 (JDP vs. MAPT). MiRNAs DE in both IL and ILLN (bta-miR-146b, bta-miR-375, bta-miR-21-5p, bta-miR-146a, bta-miR-125a, bta-miR-100, bta-miR-147, bta-miR-99a-5p, bta-miR-320 from JDP vs. HC, and bta-miR-146a, bta-let-7b from MAPT vs. HC comparisons) have roles in the immune process suggesting their potential impacts on the host response to MAP infection. The target genes of IL DE miRNAs were overrepresented in more gene ontology terms (68) while those of the ILLN were overrepresented in more pathways (20) demonstrating tissue specificity. In addition, the majority of DE miRNAs and overrepresented functional terms were unique to comparison groups and phenotypes while few were shared by two or more comparison groups and phenotype or infection status. Most of the functional terms such as cytokine receptor activity, regulation of leukocyte mediated immunity, T cell receptor signaling pathway, positive regulation of interleukin-4 production among others, have immune related functions revealing important roles of DE miRNAs in the host immune response to MAP infection. In summary, these findings underscore the pivotal regulatory roles of the identified miRNAs in shaping the host response of cows to JD. Moreover, the results indicated that mostly different sets of miRNAs, biological process and pathways were driving the JDP and MAPT phenotypes, as well as emphasize the tissue-specific nature of the miRNA response to JD, shedding light on the nuanced intricacies of host-pathogen interactions in response to MAP infection.
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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".