Sheep challenged with sheep-derived type II Mycobacterium avium subsp. paratuberculosis: the first experimental model of paratuberculosis in China
Abstract Background Paratuberculosis (PTB), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is difficult to diagnose in the early stages and poses substantial challenges in prevention, control, treatment, and eradication. A well-defined animal model can help identify disease markers and...
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BMC
2025-04-01
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| Online Access: | https://doi.org/10.1186/s12917-025-04765-1 |
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| author | Meng-Yuan Li Wei-Kang Meng Wei Ma Yu-Lin Ding Bo Yang Wei-Hong Zhao Hasi Bayaer Alateng Bagen Rui-Bin Chen Siqin Tunala Rong Zhang Chen-Guang Du Li Zhao Yong-Hong Liu |
| author_facet | Meng-Yuan Li Wei-Kang Meng Wei Ma Yu-Lin Ding Bo Yang Wei-Hong Zhao Hasi Bayaer Alateng Bagen Rui-Bin Chen Siqin Tunala Rong Zhang Chen-Guang Du Li Zhao Yong-Hong Liu |
| author_sort | Meng-Yuan Li |
| collection | DOAJ |
| description | Abstract Background Paratuberculosis (PTB), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is difficult to diagnose in the early stages and poses substantial challenges in prevention, control, treatment, and eradication. A well-defined animal model can help identify disease markers and serve as a platform for vaccine and drug development. This study used sheep as a ruminant model for experimental MAP infection research. Methods Nine 3-month-old lambs with negative MAP antigen and antibody were divided into three groups (control group A and inoculated groups B and C). The inoculated groups were challenged with sheep-derived type II MAP. After exposure, we recorded clinical signs, assessed fecal shedding, tested blood MAP levels, and performed fecal cultures. We also measured MAP-specific antibodies and monitored IFN-γ and IL-10 responses in vivo. At 255 days after inoculation, we performed autopsy, tissue culture, pathomorphological observation, and bacterial organ burden (BOB) testing. Results All six sheep in groups B and C were infected, regardless of the challenge dose and exhibited emaciation; two had intermittent soft stools. Intermittent MAP shedding in feces was observed from 60 to 255 days after exposure. Typical MAP colonies formed after 4–6 weeks of fecal and tissue culture, and Ziehl–Neelsen staining showed positive results. In the groups challenged with MAP, some blood samples tested positive for MAP and MAP-specific antibodies were detected in some serum samples. IFN-γ response was significantly higher in groups B and C than that in group A from day 60 post-exposure, whereas the IL-10 response was higher than that in group A from day 120 post-exposure. In the infected groups, the ileal lesions were the most severe and were classified as grade 3 PTB granulomatous inflammation (multibacillary lesions). BOB levels varied across different tissues. Conclusions To the best of our knowledge, this is the first experimental MAP challenge study on sheep in China. Polymerase chain reaction detection was more sensitive than MAP culture, whereas enzyme-linked immunosorbent assay was less sensitive for detecting MAP-specific antibodies. IFN-γ and IL-10 responses may serve as targets for monitoring PTB progression. The severity of ileal lesions and acid-fast bacilli grading play crucial roles in the understanding of infection dynamics. Currently, early PTB diagnosis requires a combination of multiple sample types and detection methods. |
| format | Article |
| id | doaj-art-cf47e77e5b6144c2a1a8906e65aebfac |
| institution | OA Journals |
| issn | 1746-6148 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Veterinary Research |
| spelling | doaj-art-cf47e77e5b6144c2a1a8906e65aebfac2025-08-20T01:47:32ZengBMCBMC Veterinary Research1746-61482025-04-0121111510.1186/s12917-025-04765-1Sheep challenged with sheep-derived type II Mycobacterium avium subsp. paratuberculosis: the first experimental model of paratuberculosis in ChinaMeng-Yuan Li0Wei-Kang Meng1Wei Ma2Yu-Lin Ding3Bo Yang4Wei-Hong Zhao5Hasi Bayaer6Alateng Bagen7Rui-Bin Chen8Siqin Tunala9Rong Zhang10Chen-Guang Du11Li Zhao12Yong-Hong Liu13College of Veterinary Medicine, Inner Mongolia Agricultural UniversityCollege of Veterinary Medicine, Inner Mongolia Agricultural UniversityCollege of Veterinary Medicine, Inner Mongolia Agricultural UniversityCollege of Veterinary Medicine, Inner Mongolia Agricultural UniversityAnimal Disease Control Center of OrdosCollege of Veterinary Medicine, Inner Mongolia Agricultural UniversityOtok Banner Animal Disease Prevention and Control CenterOtok Banner Animal Disease Prevention and Control CenterOtok Banner Animal Disease Prevention and Control CenterOtok Banner Animal Disease Prevention and Control CenterOtok Banner Animal Disease Prevention and Control CenterCollege of Veterinary Medicine, Inner Mongolia Agricultural UniversityCollege of Veterinary Medicine, Inner Mongolia Agricultural UniversityCollege of Veterinary Medicine, Inner Mongolia Agricultural UniversityAbstract Background Paratuberculosis (PTB), caused by Mycobacterium avium subsp. paratuberculosis (MAP), is difficult to diagnose in the early stages and poses substantial challenges in prevention, control, treatment, and eradication. A well-defined animal model can help identify disease markers and serve as a platform for vaccine and drug development. This study used sheep as a ruminant model for experimental MAP infection research. Methods Nine 3-month-old lambs with negative MAP antigen and antibody were divided into three groups (control group A and inoculated groups B and C). The inoculated groups were challenged with sheep-derived type II MAP. After exposure, we recorded clinical signs, assessed fecal shedding, tested blood MAP levels, and performed fecal cultures. We also measured MAP-specific antibodies and monitored IFN-γ and IL-10 responses in vivo. At 255 days after inoculation, we performed autopsy, tissue culture, pathomorphological observation, and bacterial organ burden (BOB) testing. Results All six sheep in groups B and C were infected, regardless of the challenge dose and exhibited emaciation; two had intermittent soft stools. Intermittent MAP shedding in feces was observed from 60 to 255 days after exposure. Typical MAP colonies formed after 4–6 weeks of fecal and tissue culture, and Ziehl–Neelsen staining showed positive results. In the groups challenged with MAP, some blood samples tested positive for MAP and MAP-specific antibodies were detected in some serum samples. IFN-γ response was significantly higher in groups B and C than that in group A from day 60 post-exposure, whereas the IL-10 response was higher than that in group A from day 120 post-exposure. In the infected groups, the ileal lesions were the most severe and were classified as grade 3 PTB granulomatous inflammation (multibacillary lesions). BOB levels varied across different tissues. Conclusions To the best of our knowledge, this is the first experimental MAP challenge study on sheep in China. Polymerase chain reaction detection was more sensitive than MAP culture, whereas enzyme-linked immunosorbent assay was less sensitive for detecting MAP-specific antibodies. IFN-γ and IL-10 responses may serve as targets for monitoring PTB progression. The severity of ileal lesions and acid-fast bacilli grading play crucial roles in the understanding of infection dynamics. Currently, early PTB diagnosis requires a combination of multiple sample types and detection methods.https://doi.org/10.1186/s12917-025-04765-1ParatuberculosisMycobacterium avium subsp. paratuberculosisSheepInfection model |
| spellingShingle | Meng-Yuan Li Wei-Kang Meng Wei Ma Yu-Lin Ding Bo Yang Wei-Hong Zhao Hasi Bayaer Alateng Bagen Rui-Bin Chen Siqin Tunala Rong Zhang Chen-Guang Du Li Zhao Yong-Hong Liu Sheep challenged with sheep-derived type II Mycobacterium avium subsp. paratuberculosis: the first experimental model of paratuberculosis in China BMC Veterinary Research Paratuberculosis Mycobacterium avium subsp. paratuberculosis Sheep Infection model |
| title | Sheep challenged with sheep-derived type II Mycobacterium avium subsp. paratuberculosis: the first experimental model of paratuberculosis in China |
| title_full | Sheep challenged with sheep-derived type II Mycobacterium avium subsp. paratuberculosis: the first experimental model of paratuberculosis in China |
| title_fullStr | Sheep challenged with sheep-derived type II Mycobacterium avium subsp. paratuberculosis: the first experimental model of paratuberculosis in China |
| title_full_unstemmed | Sheep challenged with sheep-derived type II Mycobacterium avium subsp. paratuberculosis: the first experimental model of paratuberculosis in China |
| title_short | Sheep challenged with sheep-derived type II Mycobacterium avium subsp. paratuberculosis: the first experimental model of paratuberculosis in China |
| title_sort | sheep challenged with sheep derived type ii mycobacterium avium subsp paratuberculosis the first experimental model of paratuberculosis in china |
| topic | Paratuberculosis Mycobacterium avium subsp. paratuberculosis Sheep Infection model |
| url | https://doi.org/10.1186/s12917-025-04765-1 |
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