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Master's Dissertation
DOI
10.11606/D.42.2015.tde-08062015-162010
Document
Author
Full name
Caio César Barbosa Bomfim
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2015
Supervisor
Committee
Lima, Maria Regina D'Imperio (President)
Alves Filho, José Carlos Farias
Pontillo, Alessandra
Title in Portuguese
Papel do receptor P2X7 na modulação da resposta imune pulmonar induzida por micobactérias hipervirulentas.
Keywords in Portuguese
ATP
Lesão tecidual
Micobactérias hipervirulentas
Receptor P2X7
Resposta imune
Tuberculose
Abstract in Portuguese
A tuberculose (TB) é uma doença infecciosa causada por bactérias do gênero Mycobacterium que acomete principalmente o sistema respiratório. A cepa Beijing 1471 (M. tuberculosis) induz uma resposta altamente pró-inflamatória, enquanto que a cepa MP287/03 (M. bovis) induz uma fraca resposta inflamatória. O receptor P2X7 (P2X7R) é um sensor de ATP extracelular, uma molécula associada ao dano que é liberada a partir de células necróticas. A TB induzida por ambas as cepas hipervirulentas Beijing 1471 e MP287/03 é atenuada em camundongos deficientes do P2X7R. Portanto o objetivo do nosso trabalho foi avaliar o papel do P2X7R na resposta imune da TB induzida por essas cepas hipervirulentas. Nós percebemos que apesar das diferenças na capacidade imunomodulatória induzida pelas cepas Beijing 1471 e MP287/03, o P2X7R exerce um papel importante na severidade da doença induzida por ambas as cepas, e que a ausência desse receptor foi capaz de restabelecer a resposta imune pulmonar a perfis semelhantes ao induzido pela cepa de menor virulência H37Rv de M. tuberculosis.
Title in English
Role of P2X7 receptor in modulation of lung immune response induced by hypervirulent mycobacteria.
Keywords in English
ATP
Hypervirulent mycobacteria
Immune response
P2X7 receptor
Tissue injury
Tuberculosis
Abstract in English
Tuberculosis (TB) is infectious diseases caused by Mycobacterium tuberculosis (Mtb) that mainly affect the respiratory system. Beijing 1471 strain (Mtb) induce a strong pro-inflammatory response, while MP287/03 strain (M. bovis) induce a weak pro-inflammatory response. The P2X7 receptor (P2X7R) is a sensor of extracellular ATP, a damage-associated molecule that is released from necrotic cells and that induces pro-inflammatory cytokine. TB caused by both hypervirulent strains Beijing 1471 and MP287/03 is attenuated in P2X7R deficient mice (P2X7RKO). Therefore, our aim was to investigate the role of P2X7R in imune response of TB induced by MP287/03 and Beijing 1471 strains. We has note that despite Beijing 1471 and MP287/03 strains have opposite immunomodulatory properties, the P2X7R have an important role in modulating the immune response induced by both strains. Thus, the lung immune responses induced by both hypervirulent infections in the absence of this receptor were similar to that induced by less virulent H37Rv Mtb mycobacteria.
 
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Release Date
2017-06-09
Publishing Date
2015-06-10
 
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