Evaluation of the mycobacterial virulence and modulation of the immune response during infection by clinical isolates of Mycobacterium bovis and Mycobacterium tuberculosis.

Author(s)

Eduardo Pinheiro Amaral

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
• Defense date: 2011-05-10

Examining board members

Maria Regina D\'Imperio Lima; Jose Alexandre Marzagao Barbuto; Vania Luiza Deperon Bonato Martins

• Advisor: Maria Regina D\'Imperio Lima

Abstract

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. (AU)

• FAPESP's process: 09/02696-7 - Animal model for analysis of pathogenicity of strains of Mycobacterium bovis and evaluation of the cellular and humoral immune response against pathogenic isolates
• Grantee: Eduardo Pinheiro Amaral
• Support Opportunities: Scholarships in Brazil - Master