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Doctoral Thesis
DOI
10.11606/T.87.2012.tde-18062012-095355
Document
Author
Full name
Josefa Bezerra da Silva
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2012
Supervisor
Committee
Martins, Elizabeth Angelica Leme (President)
Costa, Renata Maria Augusto da
Romero, Eliete Caló
Vasconcellos, Silvio Arruda
Vicente, Elisabete Jose
Title in Portuguese
Papel das citocinas e quimiocinas na resposta imunológica murina na infecção por Leptospira interrogans sorovar Copenhageni.
Keywords in Portuguese
Bactérias aeróbicas gram-negativas
Camundongos
Citocinas
Infecções bacterianas gram-negativas
Quimiocinas
Zoonoses por bactérias
Abstract in Portuguese
A leptospirose é uma zoonose causada por bactérias do gênero Leptospira. A patogênese da doença em humanos é observada principalmente no pulmão, fígado e rins. Neste trabalho, foi avaliado o papel da resposta imune inata na proteção contra a leptospirose usando camundongos como modelo experimental. Os animais foram infectados com L. interrogans e o desenvolvimento da doença foi acompanhado, observando-se a morte de animais C3H/HeJ, enquanto C3H/HePas apresentou icterícia e BALB/c não apresentou sintomas. O perfil de mRNA foi medido por qPCR nas amostras de rim, fígado e pulmão e as concentrações de proteinas TNF-α, TGF-b, MCP-1, MIP-1α, MIP-2 e IL-8 foram analisadas por ELISA em extratos dos tecidos e no soro. Os resultados demonstraram que L. interrogans estimula a expressão prematura de TNF-α, TGF-b, MCP-1, MIP-1α, MIP-2 e IL-8 na linhagem BALB/c resistente à infecção. A análise histológica indica que estes mediadores podem estar relacionados com o influxo de diferentes células do sistema imune desempenhando importantes funções na proteção contra leptospirose.
Title in English
The role of cytokines and chemokines in the murine immune response in infection by Leptospira interrogans serovar Copenhageni.
Keywords in English
Chemokines
Cytokines
Gram-negative aerobic bacteria
Gram-negative bacterial infections
Mice
Zoonoses by bacteria
Abstract in English
Leptospirosis is a worldwide zoonosis caused by Leptospira. The pathogenesis in humans is mainly observed in lungs, livers and kidneys. In this work the role of innate immune response in protection against leptospirosis is being studied using different mice models. The animals were infected intraperitoneally with virulent cells of L. interrogans serovar Copenhageni and the development of the disease was followed, being observed mortality of C3H/HeJ mice, whereas C3H/HePas presented jaundice and BALB/c mice remained asymptomatic. Samples of liver, kidney, lungs and sera were analyzed following the profiles of mRNA and protein of the cytokines TNF-α and TGF-b and chemokine MCP-1, MIP-1α, MIP-2 and CXCL1/IL-8. We showed that Leptospira infection stimulates early expression of cytokine TNF-α and TGF-b and chemokine MCP-1, MIP-1α, MIP-2 and IL-8 in the resistant mice strain BALB/c. Histological analysis indicates that the expression of those molecules can be related to the influx of distinct immune cells, which play a role in the naturally acquired protective immunity.
 
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Publishing Date
2012-07-06
 
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