C3HeB/FeJ mice with chronic Mycobacterium avium complex pulmonary infection exhibit impaired respiratory function but not necrotising granulomatous disease
Bibliographic record
Abstract
Abstract Background Mycobacterium avium complex (MAC) is driving a global rise in pulmonary disease (MAC-PD) characterised by chronic infection, granulomatous inflammation and impaired respiratory function. Better animal models are needed to screen candidate therapies targeting bacteria and immune-mediated tissue injury. The C3HeB/FeJ mouse was previously reported to model necrotic granulomatous lung infection in MAC-PD following infection with a low-dose inoculum of the clinical isolate MAC2285R. We investigated whether this model was reproducible with variations in MAC strain and inoculating dose. Methods Six-week-old female C3HeB/FeJ mice were infected intratracheally with a clinical isolate of MAC (MAC2285R) or reference strains (MAC104 or MAC101). Mice were culled at 4-weekly intervals post-infection until week 12. Lungs, spleen and liver were harvested for bacterial burden enumeration and histological examination. Whole body plethysmography (WBP) was performed weekly to measure changes in respiratory function (Buxco system). Results C3HeB/FeJ mice infected with low dose inoculum of MAC2285R infection exhibited increasing bacterial lung infection for 8 weeks (p < 0.05), followed by stable lung burden from weeks 8–12. High dose inoculum resulted in stable lung bacterial burden over 12 weeks. Histological analysis revealed only mild inflammatory changes in both low and high dose inoculum groups at weeks 4, 8 and 12 post-infection, with no evidence of necrotising or non-necrotising granulomatous inflammation. Surrogate measures of respiratory effort (frequency, tidal volume, inspiratory and expiratory flow rates) were increased in mice with high dose inoculum compared to uninfected controls (p < 0.001), but not low dose inoculum. Similar findings on lung bacterial burden and histological analysis were found in mice infected with low- and high-dose inoculum of MAC104 and MAC101. MAC104 infection caused greater changes in respiratory function, whereas MAC101 did not significantly affect breathing patterns. Conclusion The C3HeB/FeJ mouse is susceptible to chronic MAC infection from intratracheal infection with reference and clinical isolates, but this was not associated with severe granulomatous inflammation as previously reported. A low dose inoculum generated a proliferative lung infection, whereas high dose inoculum resulted in chronic, stable lung bacterial burden. Mice with high-dose inoculum MAC2285R and MAC104 infection also displayed evidence of increased respiratory effort.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.006 | 0.002 |
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".