Investigations of Irgm1 during experimental infections with «Mycobacterium avium paratuberculosis»
Bibliographic record
Abstract
Introduction: Mycobacterium avium paratuberculosis (MAP) is the causative agent of a chronic granulomatous enteritis of ruminants called Johne's disease (JD). Crohn's disease (CD) is an inflammatory bowel disease of unknown etiology affecting humans. Due to histological similarities between the two conditions, it has been suggested that MAP could be responsible for a subset of cases of CD. Irgm1 (murine ortholog of IRGM, a CD susceptibility gene) has been linked to host defence against mycobacteria. Methods: In the first part of this work, we have attempted to study the immune response of the Irgm1-/- mouse to systemic infection with MAP. In the second part, we have attempted to use the Irgm1-/- mouse as a host susceptible to lead to significant pathology after intra-intestinal infection with MAP (a murine model of JD) and documented its response to therapeutics used in the care of patients with CD. Results: First, we have shown that mice deleted for Irgm1 have a major susceptibility to systemic MAP infection, with accelerated rate of death and uncontrolled bacterial replication. To explain this, we have identified a defect of Irgm1-/- macrophages in controlling the intracellular growth of MAP. We have also identified severe haematological abnormalities leading to their death. Second, we have devised a protocol for the surgical inoculation of ~ 109 MAP colony forming units (CFUs) in the jejunum of Irgm1-/- mice. After 1 and 2 months of infection, we have observed significant intestinal histopathological lesions resembling those seen in Johne's disease, including focal and transmural lympho-histiocytic infiltrates and mesenteric lymphadenopathy. Mice infected according to this protocol were submitted to: 1) a systemic treatment with methylprednisolone, which did not lead to increased mortality; and 2) a treatment with an anti-tumor necrosis factor-alpha (TNF-α) antibody, which did not lead to uncontrolled MAP replication in the host.Conclusion: Irgm1-/- mice are markedly susceptible to systemic MAP infection. When inoculated with ~ 109 MAP CFUs in the lumen of the jejunum, they develop stable histological lesions resembling those of JD. Interestingly, treatments used in the cure of patients with CD did not have a deleterious effect.
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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 | 0.001 | 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".