Universidad de Buenos Aires Facultad de Ciencias...
Paratuberculosis is a chronic progressive granulomatous disease affecting ruminants, and is caused by Mycobacterium avium subsp. paratuberculosis (Map). Its worldwide distribution is known, although its prevalence remains underestimated\ndue to the difficulties derived from it diagnostic. It also ha...
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| Formato: | Tesis doctoral acceptedVersion |
| Lenguaje: | Español |
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Universidad de Buenos Aires. Facultad de Ciencias Veterinarias
2016
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| Acceso en línea: | http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=avaposgra&cl=CL1&d=HWA_1525 https://repositoriouba.sisbi.uba.ar/gsdl/collect/avaposgra/index/assoc/HWA_1525.dir/1525.PDF |
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| Sumario: | Paratuberculosis is a chronic progressive granulomatous disease affecting ruminants, and is caused by Mycobacterium avium subsp. paratuberculosis (Map). Its worldwide distribution is known, although its prevalence remains underestimated\ndue to the difficulties derived from it diagnostic. It also has economic and public\nhealth importance. In addition, the lack of preventive methods hampers its control\nand determines the existence of vacancies in research topics related with\nparatuberculosis.\nEven when Map is an intracellular bacterium, the presence of specific antibodies in the intestinal lumen at the moment of infection could modulate the host response. The aim of this thesis was to assess the effect of anti-lipoarabinomannan antibodies\n(LAM, main immunodominant exposed antigen on Map surface) on the response to\ninfection with opsonized Map of bovine macrophages (in vitro) and of calf ileal loops\n(in vivo). Antibodies were obtained from sera of healthy (n=2), paratuberculosis\nnaturally infected (n=3) or LAM-immunized (n=3) bovines. The level of apoptosis and TNF?/IL-10 secretion were measured in vitro. We found\na significant increase of the apoptosis level in macrophages when the infection took\nplace in the presence of specific antibodies (24.2 ± 2.9 % and 22.4 ± 0.9 % with\nantibodies from LAM-immunized or paratuberculosis infected bovines, respectively,\nvs. 17,2 ± 2,6 % with antibodies from healthy bovines). This effect was accompanied\nby an increase in the secretion of TNF? in both cases. For the in vivo model, ileal loops of three calves were inoculated with Map in PBS, with or without antibodies. The microscopic aspect of tissue sections, the bacterial presence and the local relative expression of TNF? and IL-10 were evaluated. As the\nmain result, a significant reduction in bacterial counts (CFU, colony forming units)\nwere detected in the presence of specific antibodies (2.6 ± 1.3 x 104 CFU/g and 0.4 ±\n0.3 x 104 CFU/g for anti-LAM and infected group vs. 5,4 ± 1,1 x 104 CFU/g for\nantibodies from healthy bovines). Overall, these findings show that specific antibodies modulate the effects of Map infection in vitro as well as in vivo in the bovine models studied here. They also demonstrate for the first time that apoptosis of macrophages can be modulated by antibodies. On reflection, it is possible to hypothesize that the presence of specific\nantibodies at the portal entry dampen Map survival after mucosal invasion, at least\npartially by promoting a pro-inflammatory environment, with TNF? predominance,\nand by increasing the apoptosis level of infected macrophages. These effects could positively impact in the mounted immune response and in the control of the\ninfection. Further research is needed in order to establish the relevance of antibody\nmediated immunity on paratuberculosis prevention in cattle. |
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