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Master's Dissertation
DOI
https://doi.org/10.11606/D.42.2011.tde-26102011-153630
Document
Author
Full name
Eduardo Pinheiro Amaral
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2011
Supervisor
Committee
Lima, Maria Regina D'Imperio (President)
Barbuto, Jose Alexandre Marzagao
Martins, Vania Luiza Deperon Bonato
Title in Portuguese
Avaliação da virulência micobacteriana e modulação da resposta imune durante a infecção por isolados clínicos de Mycobacterium bovis e Mycobacterium tuberculosis.
Keywords in Portuguese
Mycobacterium bovis
Mycobacterium tuberculosis
Adjuvantes imunológicos
Citocinas
Infecções bacterianas
Virulência
Abstract in Portuguese
A tuberculose é considerada um problema emergente de saúde pública. Este estudo tem como objetivo avaliar a associação da patogenicidade/virulência e propriedades imunomoduladoras de isolados clínicos de Mbv (cepas B2 e MP287/03) e Mtb (cepa Beijing 1471), e da cepa de Mtb H37Rv, como referência de virulência. Os isolados, MP287/03 e Beijing 1471, apresentaram maior virulência em relação às demais cepas, levando os camundongos à morte ainda na fase aguda de infecção. Foi verificada baixa produção de mediadores pró-inflamatórios nos animais infectados com o isolado MP287/03, enquanto nos infectados com o isolado Beijing 1471 os níveis destes mediadores foram exacerbados. O desbalanço na produção destes mediadores pode ter contribuído para morte precoce dos animais. Baseado nesse estudo, nós podemos concluir que as propriedades que conferem hipervirulência aos isolados clínicos de Mbv e Mtb estão principalmente relacionadas à alta capacidade de crescimento intracelular das bactérias, que parece ser pouco alterada pela presença de citocinas pró-inflamatórias. Sendo assim, as infecções por isolados hipervirulentos podem acarretar consequências semelhantes, mesmo quando associadas a diferentes padrões de modulação da resposta imune.
Title in English
Evaluation of the mycobacterial virulence and modulation of the immune response during infection by clinical isolates of Mycobacterium bovis and Mycobacterium tuberculosis.
Keywords in English
Mycobacterium bovis
Mycobacterium tuberculosis
Bacterial infections
Cytokines
Immune adjuvants
Virulence
Abstract in English
Tuberculosis is an emergent problem of public health. This study aimed to evaluate the association between pathogenicity/virulence and immunemodulatory ability of Mbv (B2 and MP287/03) and Mtb (Beijing 1471) clinical isolates, using H37Rv strain as reference of virulence. The virulence was assessed in C57BL/6 mice infected with a low dose of bacilli (~100 bacteria) via intratracheal route. MP287/03 and Beijing 1471 isolates showed higher virulence than all others strains, leading to mice death during the acute phase. It was verified low production of pro-inflammatory mediators in mice infected by MP287/03 bacteria, whereas in mice infected by Beijing 1471 bacteria were observed exacerbated levels of pro-inflammatory mediators. The disbalance of these mediators may have contributed to the early mouse death. Based on this study, we concluded that the properties that confer hypervirulence to Mbv and Mtb clinical isolates are primarily related to the high intracellular growth capacity of the bacteria, which seems to be marginally affected by the presence of pro-inflammatory cytokines. Therefore, the infection by hypervirulent isolates can lead to similar outcomes, even when associated to different patterns of modulation of the immune response.
 
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Publishing Date
2011-11-11
 
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