Challenge Dose Titration in a Mycobacterium bovis Infection Model in Goats
Abstract
:1. Introduction
2. Results
2.1. Clinical Investigation of M. bovis-Inoculated Goats
2.2. Results of Intra Vitam Testing for Indications of Mycobacterial Infection
2.3. Quantitation of M. bovis Antigen-Specific T Cells After In Vitro Re-Stimulation
2.4. Shedding of the Inoculum Strain via Nose and Feces
2.5. Computed Tomography Imaging (CT) of Lungs from M. bovis-Inoculated Goats
2.6. Macroscopic and Histologic Lesions, and Detection of Acid-Fast Bacilli in Tissues from M. bovis-Inoculated Goats
2.7. Dissemination of the Inoculum Strain in the Body
3. Discussion
4. Materials and Methods
4.1. Animals, Housing Conditions and Nutrition Regime
4.2. Legislation and Ethical Approval
4.3. Inoculum and Inoculation
4.4. Clinical Examination and Intra Vitam Sampling
4.5. Intra Vitam Testing for Indications of Mycobacterial Infection
4.6. Quantitation of Intracellular IFN-γ in CD4+, CD8+ and γδ T Cells after In Vitro-Stimulation with Specific Antigen
4.7. Quantitation of Antigen-Specific Peripheral T Cells by Activation Marker Expression Analysis after In Vitro Stimulation with Specific Antigens
4.8. Euthanasia, Necropsy, Gross Pathology, Tissue Sampling
4.9. Radiological Examination by Computed Tomography (CT)
4.10. Histologic Examination
4.11. Bacterial Examination of Feces, Nasal Swabs and Tissue Samples
4.12. Statistical Analysis
5. Patents
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Group | Goat | Cranial Tracheo-Bronchial LNs | Left Tracheo-Bronchial LNs * | Right Tracheo-Bronchial LNs | Mid Tracheo-Bronchial LNs | Pulmonary LNs |
---|---|---|---|---|---|---|
low dose | 5 | ++ | +++ | +++ | - | - |
6 | +++ | ++ | - | ++ | - | |
7 | +++ | - | - | +++ | - | |
8 | +++ | +++ | +++ | ++ | + | |
medium dose | 9 | ++ | + | + | + | - |
10 | +++ | ++ | - | - | + | |
11 | +++ | ++ | ++ | - | ++ | |
12 | +++ | + | - | - | - | |
high dose | 13 | +++ | ++ | ++ | ++ | - |
14 | ++ | ++ | +++ | - | + | |
15 | +++ | +++ | +++ | ++ | - |
Group | Goat | Head LNs and Tonsils | Respir. Tract | Large Parenchyma | Gastrointestinal Tract | Other Sites | ||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 A | 11 | 12 | 13 | 14 | 15 | 16 | 17 | 18 | 19 | 20 | 21 | 22 | 23 | ||
control | 1 to 4 | |||||||||||||||||||||||
low dose | 5 | + | ⊕ | + | ||||||||||||||||||||
6 | ⊕ | ⊕ | + | O | ||||||||||||||||||||
7 | ⊕ | ⊕ | + | |||||||||||||||||||||
8 | O | O | ⊕ | ⊕ | + | O | ⊕ | ⊕ | ⊕ | |||||||||||||||
medium dose | 9 | O | O | ⊕ | O | + | ⊕ | ⊕ | O | O | ||||||||||||||
10 | ⊕ | + | ⊕ | |||||||||||||||||||||
11 | ⊕ | ⊕ | + | |||||||||||||||||||||
12 | + | + | + | |||||||||||||||||||||
high dose | 13 | ⊕ | ⊕ | + | ⊕ | + | ||||||||||||||||||
14 | O | ⊕ | ⊕ | ⊕ | ⊕ | + | O | ⊕ | ⊕ | + A | ⊕ | ⊕ | ||||||||||||
15 | O | + | ⊕ | ⊕ | + | ⊕ | ⊕ | ⊕ | + B | + A | ⊕ | O | O C pharyngeal tonsils, + A pleura | |||||||||||
16 D | + | ⊕ | + | ⊕ inj. site trachea | ||||||||||||||||||||
1 left mandibular LN | 6 left medial retroph. LN | 11 liver | 16 bone marrow | 21 mesenteric LNs | ||||||||||||||||||||
2 right mandibular LN | 7 right medial retroph. LN | 12 hepatic LNs | 17 heart | 22 ileocolic LNs | ||||||||||||||||||||
3 left parotid LN | 8 left tracheobronchial LN | 13 spleen | 18 JPP | 23 other sites | ||||||||||||||||||||
4 right parotid LN | 9 mediastinal LNs | 14 kidney | 19 IPP | |||||||||||||||||||||
5 palatine tonsil | 10 lung | 15 renal LNs | 20 other GALT |
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Liebler-Tenorio, E.M.; Wedlich, N.; Figl, J.; Koehler, H.; Ulrich, R.; Schröder, C.; Rissmann, M.; Grode, L.; Kaufmann, S.H.E.; Menge, C. Challenge Dose Titration in a Mycobacterium bovis Infection Model in Goats. Int. J. Mol. Sci. 2024, 25, 9799. https://doi.org/10.3390/ijms25189799
Liebler-Tenorio EM, Wedlich N, Figl J, Koehler H, Ulrich R, Schröder C, Rissmann M, Grode L, Kaufmann SHE, Menge C. Challenge Dose Titration in a Mycobacterium bovis Infection Model in Goats. International Journal of Molecular Sciences. 2024; 25(18):9799. https://doi.org/10.3390/ijms25189799
Chicago/Turabian StyleLiebler-Tenorio, Elisabeth M., Nadine Wedlich, Julia Figl, Heike Koehler, Reiner Ulrich, Charlotte Schröder, Melanie Rissmann, Leander Grode, Stefan H. E. Kaufmann, and Christian Menge. 2024. "Challenge Dose Titration in a Mycobacterium bovis Infection Model in Goats" International Journal of Molecular Sciences 25, no. 18: 9799. https://doi.org/10.3390/ijms25189799