Challenge Dose Titration in a Mycobacterium bovis Infection Model in Goats.

Autor: Liebler-Tenorio EM; Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, 07743 Jena, Germany., Wedlich N; Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, 07743 Jena, Germany., Figl J; Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, 07743 Jena, Germany., Köhler H; Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, 07743 Jena, Germany., Ulrich R; Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany., Schröder C; Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany., Rissmann M; Department of Experimental Animal Facilities and Biorisk Management, Friedrich-Loeffler-Institut, 17493 Greifswald, Germany., Grode L; Serum Life Science Europe GmbH, 30659 Hannover, Germany., Kaufmann SHE; Max Planck Institute for Infection Biology, 10117 Berlin, Germany.; Max Planck Institute for Multidisciplinary Sciences, 37077 Göttingen, Germany.; Hagler Institute for Advanced Study, Texas A&M University, College Station, TX 77843, USA., Menge C; Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut, 07743 Jena, Germany.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2024 Sep 10; Vol. 25 (18). Date of Electronic Publication: 2024 Sep 10.
DOI: 10.3390/ijms25189799
Abstrakt: Goats are natural hosts of Mycobacterium (M.) bovis , and affected herds can be the cause of significant economic losses. Similarites in disease course and lesions of M. bovis infections in goats and M. tuberculosis in humans make goats good models for human tuberculosis. The aim of this investigation was to characterize M. bovis challenge models in goats. For this, goats were endobronchially inoculated with three doses of M. bovis or culture medium. Clinical signs, shedding, and immune responses were monitored until 146 days post inoculation (dpi). At necropsy, lesions were examined by computed tomography, histology, and bacteriological culture. Infected goats did not develop clinical signs. M. bovis was cultured from feces, but never from nasal swabs. IGRAs were positive from 28 dpi onwards, antibodies at 140 dpi, and SICCT at 146 dpi. The increase in CD25 + , IFN-γ + , and IFN-γ-releasing T-cell subpopulations was time-related, but not dose-dependent. All infected goats developed paucibacillary granulomas in the lungs and regional lymph nodes. M. bovis was regularly cultured. Dose-dependent effects included the size of pulmonary lesions, caverns, intestinal lesions, and early generalization in the high-dose group. In summary, reproducible challenge models with dose-dependent differences in lesions were established, which may serve for testing vaccines for veterinary or medical use.
Databáze: MEDLINE