Bovine TB: Research project summary
Project SE3027: Pathogenesis and immunology of Mycobacterium bovis infection in cattle
Project duration: 3 years
The aim of this project was to analyse the mechanisms of immunity to Mycobacterium bovis (M. bovis) in cattle. Cellular immune responses and the pathological response to virulent M. bovis, avirulent BCG and the potential impacts of prior exposure to environmental mycobacteria were analysed.
The effects of infection with M. bovis or BCG on antigen presenting cell (APC) function were assessed. Different types of APC showed divergent responses. Thus, M. bovis survived better inside dendritic cells compared to macrophages, and the cytokines secreted differed between the two cell types. The survival of BCG was lower than that of M. bovis and cytokine induction was weak. These data suggested that the initial interaction of M. bovis with APC could be pivotal in determining the outcome of infection. Within lymph nodes from infected animals down-regulation of pro and anti-inflammatory cytokine expression was observed which may aid bacterial survival.
Both CD4+ and CD8+ T lymphocytes
were shown to be involved in the response to M. bovis infection
through IFN0 secretion. In addition, NK cells were shown to react to M.
bovis infected dendritic cells and could be involved in early responses
in vivo by secreting IFN0.
Prior exposure to Mycobacterium avium (as a model for environmental
mycobacteria) gave partial protection against M. bovis infection.
However, diagnosis by the skin test or IFN0 test was compromised. Similar
results were obtained in animals exposed to M. avium prior to
BCG followed by M. bovis challenge; no additional protective
effects compared to BCG alone were observed and diagnostic tests were
compromised in the animals pre-exposed to M. avium. Use of ESAT-6
and CFP-10 was more effective than PPD for detecting tuberculosis in animals
previously exposed to M. avium, but was not effective in some
cases. Responses to DNA vaccination were not affected by the inclusion
of the cytokine IL-12, even after a BCG boost. Vaccination of animals
at different ages with BCG indicated that neonatal vaccination is an effective
strategy significantly reducing pathology and bacterial load. Neonatal
vaccination in the field prior to exposure to environmental mycobacteria
would potentially maximise the protective efficacy of BCG.
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July 7, 2008