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Master's Dissertation
DOI
10.11606/D.42.2014.tde-12082014-153344
Document
Author
Full name
Leandro Carvalho Dantas Breda
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2014
Supervisor
Committee
Isaac, Lourdes (President)
Carvalho, Enéas de
Starobinas, Nancy
Title in Portuguese
Mecanismos de evasão do sistema complemento por Leptospira ssp.: interação com inibidor de C1 esterase e C4BP.
Keywords in Portuguese
C1INH
C4BP
Leptospira
LigA
LigB
Abstract in Portuguese
O sistema complemento (SC) é um importante componente da imunidade inata na eliminação de patógenos. Suas proteínas reguladoras são necessárias para controlar a excessiva ativação sobre células próprias. Porém, alguns patógenos ligam a estas proteínas reguladoras para escapar do SC. A Leptospira spp. - agente etiológico do leptospirose - interage com Fator H e C4BP permitindo a evasão ao SC. As regiões SCR 7 e 8 da C4BP são responsáveis pela interação com proteínas LcpA e LigBC, e os SCRs 4, 7 e 8 são responsáveis pela interação com LigAC e L. interrogans íntegra. Estas interaçôes são dependentes de forças iônicas e inibidas por heparina. Outro importante regulador da via clássica e das lectinas é o inibidor de C1 esterase. Observamos sua a interação com leptospira atenuada, patogênica e não patogênica. Ensaios de sobrevivência de leptospira sugerem sua importância na sobrevida de leptospira atenuada, podendo ser utilizado como mecanismo de escape à via clássica e das lectinas do SC, sendo o primeiro mecanismo deste tipo, investigado em leptospiras.
Title in English
Immune evasion mechanisms by Leptospiras spp.: interaction with C1 esterase inhibitor and C4b-binding protein.
Keywords in English
C1INH
C4BP
Leptospira
LigA
LigB
Abstract in English
Leptospirosis is a zoonosis caused by bacteria Leptospira. The Complement System plays a crucial role in the immune response against Leptospira. Non-pathogenic leptospira is eliminated by complement while pathogenic is able to avoid complement activation by the acquisition of host complement inhibitors Factor H and C4BP. We verified that SCR 7 and 8 of C4BP alpha chain are responsible to interaction with outer membrane proteins of L. interrogans LcpA and LigBC while SCR 4, 7 and 8 are responsible to interaction with LigAC and L. interrogans. We characterized this protein-protein interaction and verified that is ionic strength dependent and is inhibited by heparin. C1INH, another important regulator of classical and lectin pathways, interacts with the surface of leptospiras pathogenic, non-patogenic and attenuated and it is still able to regulates the classical pathway. We also performed a killing experiment and verified that C1INH is important to the survival of leptospiras attenuated, been the first complement system evasion mechanisms verified at this strain.
 
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Publishing Date
2014-08-12
 
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