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Doctoral Thesis
DOI
10.11606/T.87.2008.tde-10032009-130929
Document
Author
Full name
Ana Paula Guarnieri Christ
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Leite, Luciana Cezar de Cerqueira (President)
Barbuto, Jose Alexandre Marzagao
Oliveira, Sergio Costa
Saldiva, Paulo Hilario Nascimento
Vargaftig, Bernardo Boris Jorge
Title in Portuguese
Modulação da resposta alérgica por BCG recombinante em modelo murino de asma.
Keywords in Portuguese
Alergia
Asma
BCG recombinante
Citocina IFNg
Pulmão
TH1
Abstract in Portuguese
Asma alérgica é uma inflamação pulmonar crônica mediada por células Th2. A Hipótese da Higiene é a teoria aceita para explicar o aumento das alergias nas últimas décadas e preconiza que a menor exposição dos indivíduos a componentes microbianos prejudica a geração mecanismos imunorregulatórios. Nosso estudo abordou a modulação da resposta alérgica pulmonar induzida por ovalbumina, por cepas de bacilo Calmette-Guérin recombinantes (rBCG) que expressam fragmentos de toxinas bacterianas. Observamos que dependendo do antígeno heterólogo expresso, a imunização intranasal com rBCG pode levar tanto a supressão como a exacerbação da resposta alérgica pulmonar. Demonstramos que tanto em um contexto profilático quanto terapêutico, rBCG é capaz de suprimir os parâmetros alérgicos, e a supressão não envolve o recrutamento de células T regulatórias, é um fenômeno local, está associada a maior produção de IFN-g do que IL-4 e é dependente de IL-12. Estes dados sugerem que a infecção pulmonar por rBCG gera um milieu capaz de bloquear a migração de células Th2 inflamatórias.
Title in English
Modulation of allergic immue responses by recombinant BCG in a murine model of asthma.
Keywords in English
Allergy
Asthma
IFNg cytokine
Lung
Recombinant BCG
TH1
Abstract in English
Allergic asthma is an atopic disorder mediated by Th2 cells. The Hygiene Hypothesis is the accepted theory to explain the increasing in allergy in recent deacades. It states that modern health care and hygiene practices have led to a reduced exposure to microorganisms components which impairs the generation of immunoregulatory mechanisms. The present study analysed how the intranasal infection with recombinant bacillus Calmette-Guérin (rBCG) strains expressing fragments of bacterial toxins could modulate an allergic pulmonary inflammation induced by ovalbumin. We demonstrated that the rBCG strains could supress or exacerbate the allergic inflammation depending on the expressed heterologous antigen. We analysed the effect of the mycobacterial infection in a prophylactic and in a therapeutical contexts, and we have identified that for both situations the of supression allergic features does not involve the recruitment of regulatory T cells to the lungs, is a local phenomena, is associated with an increased production of IFN-g, and is an IL-12 dependent mechanism. Taken togheter, this data suggest that the rBCG pulmonary infection generates a milieu capable to supress the chemotaxis for Th2 cells, which suppress the establishment of the allergic inflammation in the lungs.
 
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Anexo_1.pdf (2.08 Mbytes)
Anexo_2.pdf (210.36 Kbytes)
Anexo_3.pdf (1.05 Mbytes)
Publishing Date
2009-03-19
 
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