Histopathological and Morphometrical Comparison of Granulomatous Lesions in BALB/c and C3H/HeJ Mice Inoculated with Mycobacterium paratuberculosis

Tanaka, Shogo; Sato, Mariko; Taniguchi, Toshiaki; Yokomizo, Yuichi

doi:10.1016/s0021-9975(08)80315-5

Cited by 33 publications

(35 citation statements)

References 8 publications

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“…Also, mice with variable genetic background are readily available, allowing investigation of host-pathogen interactions on a molecular level. In numerous studies (Shin et al, 2006;Stabel and Ackermann, 2002;Tanaka et al, 1994) histological and immunological features reproduced in mice were generally similar to those in ruminants (Table 6). Generally, the degree of bacterial colonization and the type of cells recruited to granulomatous lesions depend on the mouse genetic background as well as virulence of the mycobacterial strain (Mullerad et al, 2002;Shin et al, 2006;Tanaka et al, 1994), indicating the utility of the murine model in elucidation of pathogenetic mechanisms.…”

Section: Long-term Murine Map Challenge Modelmentioning

confidence: 62%

“…Some studies used BALB/c or C57/ BL6 strains which are immune-competent, but susceptible to infection (Veazey et al, 1995). Others used C3H mice, which are more resistant (Tanaka et al, 1994). Despite the presence of granulomatous lesions in both susceptible and resistant strains of mice, the number of lesions and degree of bacterial colonization declined dramatically in the resistant strain.…”

Section: Long-term Murine Map Challenge Modelmentioning

confidence: 99%

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Experimental challenge models for Johne's disease: A review and proposed international guidelines

Hines

Stabel

Sweeney

et al. 2007

Veterinary Microbiology

123

140

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An international committee of Johne's disease (JD) researchers was convened to develop guidelines for JD challenge studies in multiple animal species. The intent was to develop and propose international standard guidelines for models based on animal species that would gain acceptance worldwide. Parameters essential for the development of long-term and short-term infection models were outlined and harmonized to provide a ''best fit'' JD challenge model for cattle, goats, sheep, cervids, and mice. These models will be useful to study host-pathogen interactions, host immunity at the local and systemic level, and for evaluating vaccine candidates and therapeutics. The consensus guidelines herein list by animal species strains of Mycobacterium avium subsp. paratuberculosis used, challenge dose, dose frequency, age of challenge, route of challenge, preparation of inoculum, experimental animal selection, quality control, minimal experimental endpoints and other parameters. #

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Section: Long-term Murine Map Challenge Modelmentioning

confidence: 62%

Section: Long-term Murine Map Challenge Modelmentioning

confidence: 99%

Experimental challenge models for Johne's disease: A review and proposed international guidelines

Hines

Stabel

Sweeney

et al. 2007

Veterinary Microbiology

123

140

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“…Mice are cost effective, present some histological and immunological features similar to those of ruminants, and can serve as a preliminary screening model for vaccine candidates (39,41), but they do not develop disease typical of that seen with ruminants with paratuberculosis (9,41). In comparison, goats are much more costly but provide a direct homologue of the disease in cattle and other ruminants, which is beneficial for pathogenesis and vaccine efficacy studies (21,32).…”

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confidence: 99%

Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

et al. 2010

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Mycobacterium avium subsp. paratuberculosis (basonym M. paratuberculosis) is the causative agent of paratuberculosis, a chronic enteritis of ruminants. To control the considerable economic effect that paratuberculosis has on the livestock industry, a vaccine that induces protection with minimal side effects is required. We employed transposon mutagenesis and allelic exchange to develop three potential vaccine candidates, which were then tested for virulence with macrophages, mice, and goats. All three models identified the WAg906 mutant as being the most attenuated, but some differences in the levels of attenuation were evident among the models when testing the other strains. In a preliminary mouse vaccine experiment, limited protection was induced by WAg915, as evidenced by a reduced bacterial load in spleens and livers 12 weeks following intraperitoneal challenge with M. paratuberculosis K10. While we found macrophages and murine models to be rapid and cost-effective alternatives for the initial screening of M. paratuberculosis mutants for attenuation, it appears necessary to do the definitive assessment of attenuation with a ruminant model.

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“…To reduce the cost associated with investigation of JD in cattle, several nonbovine infection models have been used, none of which provides a complete clinical picture of JD. For example, to simulate the granulomatous enteritis aspect of JD, both immune-competent (38) and immune-compromised (12,25) mouse models have been successfully employed to model the chronic features of M. avium subsp. paratuberculosis infection.…”

mentioning

confidence: 99%

Invasion and Persistence ofMycobacterium aviumsubsp.paratuberculosisduring Early Stages of Johne's Disease in Calves

Wu¹,

Livesey

Schmoller³

et al. 2007

Infect Immun

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Infection with Mycobacterium avium subsp. paratuberculosis causes Johne's disease in cattle and is a serious problem for the dairy industry worldwide. Development of models to mimic aspects of Johne's disease remains an elusive goal because of the chronic nature of the disease. In this report, we describe a surgical approach employed to characterize the very early stages of infection of calves with M. avium subsp. paratuberculosis. To our surprise, strains of M. avium subsp. paratuberculosis were able to traverse the intestinal tissues within 1 h of infection in order to colonize distant organs, such as the liver and lymph nodes. Both the ileum and the mesenteric lymph nodes were persistently infected for months following intestinal deposition of M. avium subsp. paratuberculosis despite a lack of fecal shedding of mycobacteria. During the first 9 months of infection, humoral immune responses were not detected. Nonetheless, using flow cytometric analysis, we detected a significant change in the cells participating in the inflammatory responses of infected calves compared to cells in a control animal. Additionally, the levels of cytokines detected in both the ileum and the lymph nodes indicated that there were TH1-type-associated cellular responses but not TH2-type-associated humoral responses. Finally, surgical inoculation of a wild-type strain and a mutant M. avium subsp. paratuberculosis strain (with an inactivated gcpE gene) demonstrated the ability of the model which we developed to differentiate between the wild-type strain and a mutant strain of M. avium subsp. paratuberculosis deficient in tissue colonization and invasion. Overall, novel insights into the early stages of Johne's disease were obtained, and a practical model of mycobacterial invasiveness was developed. A similar approach can be used for other enteric bacteria.Johne's disease (JD) or paratuberculosis in cattle is caused by Mycobacterium avium subsp. paratuberculosis. Virtually all ruminants are believed to be susceptible to infection with this organism, which causes severe economic losses estimated to be around $200 to $250 million a year for the dairy industry in the United States alone (19). Worldwide, the prevalence of the infection can range from 3 to 4% in herds (e.g., in England) (4) to as much as 50% in herds (e.g., in Wisconsin and Alabama) (6,14). A recent report by members of the National Research Council on the status of JD stressed the need to fill several gaps in our knowledge associated with the pathophysiology, immunology, and control of JD (7). JD research is hampered by the low growth rate of M. avium subsp. paratuberculosis and the lack of a reliable animal model to investigate host-pathogen interactions. Despite the introduction of molecular protocols to facilitate JD diagnosis (11, 39), the tools that are available are unreliable for detection of infected cows, especially cows in the early stages of infection (5). Currently, no effective treatment regimen is available, and the control strategies for afflicted herds are bas...

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Histopathological and Morphometrical Comparison of Granulomatous Lesions in BALB/c and C3H/HeJ Mice Inoculated with Mycobacterium paratuberculosis

Cited by 33 publications

References 8 publications

Experimental challenge models for Johne's disease: A review and proposed international guidelines

Experimental challenge models for Johne's disease: A review and proposed international guidelines

Assessment of Live Candidate Vaccines for Paratuberculosis in Animal Models and Macrophages

Invasion and Persistence ofMycobacterium aviumsubsp.paratuberculosisduring Early Stages of Johne's Disease in Calves

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