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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I28-R145-HWA_1525 |
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dspace |
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Universidad de Buenos Aires |
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I-28 |
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R-145 |
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Repositorio Digital de la Universidad de Buenos Aires (UBA) |
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Español |
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spa |
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Paratuberculosis Micobacterias ¨Bovino Anticuerpos Funcionalidad Bovinos Paratuberculosis Anticuerpos anti-arabinomanano Infección bacteriana Inmunología |
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Paratuberculosis Micobacterias ¨Bovino Anticuerpos Funcionalidad Bovinos Paratuberculosis Anticuerpos anti-arabinomanano Infección bacteriana Inmunología Jolly, Ana Universidad de Buenos Aires Facultad de Ciencias... |
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Paratuberculosis Micobacterias ¨Bovino Anticuerpos Funcionalidad Bovinos Paratuberculosis Anticuerpos anti-arabinomanano Infección bacteriana Inmunología |
| description |
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. |
| author2 |
Hajos, Silvia Elvira |
| author_facet |
Hajos, Silvia Elvira Jolly, Ana |
| format |
Tesis doctoral Tesis doctoral acceptedVersion |
| author |
Jolly, Ana |
| author_sort |
Jolly, Ana |
| title |
Universidad de Buenos Aires Facultad de Ciencias... |
| title_short |
Universidad de Buenos Aires Facultad de Ciencias... |
| title_full |
Universidad de Buenos Aires Facultad de Ciencias... |
| title_fullStr |
Universidad de Buenos Aires Facultad de Ciencias... |
| title_full_unstemmed |
Universidad de Buenos Aires Facultad de Ciencias... |
| title_sort |
universidad de buenos aires facultad de ciencias... |
| publisher |
Universidad de Buenos Aires. Facultad de Ciencias Veterinarias |
| publishDate |
2016 |
| url |
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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AT jollyana universidaddebuenosairesfacultaddeciencias AT jollyana paratuberculosisbovinafunciondelosanticuerposantilipoarabinomananoenlainfeccion |
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1824356436330676224 |
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I28-R145-HWA_15252024-08-27 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 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. Fil: Jolly, Ana. Universidad de Buenos Aires. Facultad de Ciencias Veterinarias. Buenos Aires, Argentina Hajos, Silvia Elvira Mundo, Silvia Leonor Jolly, Ana 2016-12-05 La paratuberculosis es una enfermedad granulomatosa, progresiva y crónica de\nlos rumiantes causada por Mycobacterium avium subsp. paratuberculosis (Map). Si bien su presentación es endémica a nivel mundial, su prevalencia está subestimada por las limitantes asociadas al diagnóstico. Presenta importancia en Salud Pública y fuerte impacto económico. Esto sumado a la carencia de medidas eficaces para su\nprevención, hacen de la paratuberculosis una enfermedad con muchos temas vacantes en materia de investigación. Si bien Map es un patógeno intracelular, la presencia de anticuerpos específicos\nen la luz intestinal al momento de la infección podría modular la respuesta del huésped. El objetivo de esta tesis fue evaluar el efecto de la opsonización de Map con anticuerpos anti-lipoaraninomanano (LAM, antígeno inmunodominante de superficie de Map) sobre la respuesta a la infección de macrófagos bovinos (in vitro) y de segmentos intestinales en terneros (in vivo). En ambos modelos, se emplearon anticuerpos séricos de bovinos sanos (n=2), con paratuberculosis natural (n=3) o\ninmunizados con LAM (n=3) para pretratar Map.\nEn los experimentos in vitro, las variables estudiadas fueron el nivel de apoptosis y de secreción de TNF? e IL-10. Encontramos que la presencia de anticuerpos\nespecíficos incrementó significativamente la apoptosis de los macrófagos infectados. Por ejemplo, obtuvimos valores de 24,2 ± 2,9 % y de 22,4 ± 0,9 % al preincubar Map con anticuerpos de bovinos inmunizados con LAM o infectados, mientras que el\nporcentaje de apoptosis en presencia de anticuerpos de bovinos sanos fue de 17,2 ±\n2,6 %. Este efecto estuvo acompañado por un incremento significativo del nivel de secreción de TNF? en ambos casos. Para el modelo in vivo, se realizó la infección quirúrgica de segmentos intestinales\nde 3 terneros con: Map en PBS, o preincubada con anticuerpos. Se evaluó el aspecto microscópico de los cortes tisulares, la presencia bacteriana y los niveles relativos de expresión de TNF? e IL-10, a las 3,5 horas post-infección. Como principal resultado\nencontramos una diferencia significativa en el nivel de recuperación bacteriana a\npartir de los segmentos infectados con los diferentes anticuerpos. Cuando la\ninfección se produjo en presencia de anticuerpos específicos hubo una reducción significativa de las Unidades Formadoras de Colonias (UFC) recuperadas, tanto con\nlos obtenidos de bovinos inmunizados con LAM como de infectados (2,6 ± 1,3 x 104 y 0,4 ± 0,3 x 104, respectivamente, vs. 5,4 ± 1,1 x 104 UFC/g tejido, para los segmentos inoculados en presencia de anticuerpos de bovinos sanos).En conjunto, los resultados de esta tesis indican que los anticuerpos específicos modulan los efectos de la infección por Map, tanto in vitro como in vivo, en los modelos bovinos estudiados. Asimismo, postulan por primera vez la capacidad de los\nanticuerpos de modular la apoptosis de macrófagos. A modo de reflexión final, es\nposible hipotetizar que la presencia local de altos niveles de anticuerpos específicos al momento de la infección natural por Map podría afectar la supervivencia\nbacteriana en el intestino, en parte por su contribución para el desarrollo de un\nmicroambiente pro-inflamatorio, con predominio de TNF? y por el incremento de los niveles de apoptosis de los macrófagos infectados. Estos efectos tendrían un impacto\npositivo sobre la respuesta inmune en desarrollo y sobre el control de la infección. Es necesario continuar nuestras investigaciones a fin de establecer la relevancia de la inmunidad mediada por anticuerpos en la prevención de la paratuberculosis bovina. application/pdf Paratuberculosis Micobacterias ¨Bovino Anticuerpos Funcionalidad spa Universidad de Buenos Aires. Facultad de Ciencias Veterinarias info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by-nc-nd/2.5/ar/ Bovinos Paratuberculosis Anticuerpos anti-arabinomanano Infección bacteriana Inmunología Inmunología Doctora de la Universidad de Buenos Aires Paratuberculosis bovina : función de los anticuerpos antilipoarabinomanano en la infección info:eu-repo/semantics/doctoralThesis info:ar-repo/semantics/tesis doctoral info:eu-repo/semantics/acceptedVersion 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 |