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Doctoral Thesis
DOI
10.11606/T.5.2016.tde-20092016-155050
Document
Author
Full name
Mariana Macedo Costa de Andrade
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2016
Supervisor
Committee
Soriano, Francisco Garcia (President)
Silva, Fabiano Pinheiro da
Pinho, João Renato Rebello
Souza, Heraldo Possolo de
Vasconcelos, Dewton de Moraes
Title in Portuguese
O efeito da tolerância à endotoxina nos linfócitos T regulatórios e Th 17
Keywords in Portuguese
Células Th17
Inflamação
Linfócitos T reguladores
Sepse
Tolerância
Abstract in Portuguese
O controle de respostas imunes patológicas (autoimunidade, alergia, rejeição de transplantes) tem sido um dos principais objetivos dos imunologistas. Apesar dos avanços recentes, a maioria dos tratamentos atuais ainda procura diminuir a imunidade e inflamação em vez de restabelecer o estado saudável da tolerância imunológica. Sepse é uma doença desencadeada pela presença de bactérias e/ou produtos bacterianos como lipopolissacarídeos (LPS), componente principal da membrana externa de bactérias gram-negativas, ativando a resposta imune do hospedeiro. A caracterização do perfil de linfócitos na resposta à tolerância ao LPS são de extrema importância para a contribuição do estudo da imunodepressão na sepse. O objetivo deste estudo foi investigar se a comprovada redução de mortalidade previamente vista em modelo de sepse animal através tolerância ao LPS, pode ser associada com o aumento da população de linfócitos T CD4+ regulatórios e Th17. Camundongos machos C57/6, receberam por via subcutânea ( s.c.) injecções de LPS ( 1mg/kg ) durante 5 dias , seguido por perfuração e ligadura cecal (CLP ) . Citocinas e linfócitos marcados foram medidos durante, após a tolerância e o desafio CLP. Ambos os subtipos de células T analisados Treg e Th17 , mostrou aumento destas células no baço durante e após a tolerância. Este estudo demonstrou que a mortalidade reduzida depois de tolerância previamente constatada pode ser associada com o aumento da população de células T regulatórias e Th17 devido a imunorregulação do hiperinflamação e recrutamento de neutrófilos
Title in English
The effect of endotoxin tolerance in lymphocytes regulatory and Th17
Keywords in English
Inflammation
Regulatory T-lymphocytes
Sepsis
Th17 cells
Tolerance
Abstract in English
The control of pathological immune responses (autoimmunity, allergy, transplant rejection) has been a major goal of immunologists. Despite recent advances, most current treatments still seeks to reduce immunity and inflammation rather than restore the healthy state of immune tolerance. Sepsis is a disease triggered by the presence of bacteria and / or bacterial products like lipopolysaccharide (LPS), the main component of the outer membrane of gram-negative bacteria, activating the immune response of the host. The characterization of lymphocyte profile in response to LPS tolerance is extremely important for the study of immunosuppression in sepsis contribution. The aim of this study was to investigate whether the proven reduction in mortality seen previously in animal sepsis model by tolerance to LPS, can be associated with the increase in population of CD4 + regulatory and Th17. Mice C57 / 6 mice received subcutaneous (s.c.) injection of LPS (1mg / kg) for 5 days, followed by cecal ligation and puncture (CLP). Cytokines and marked lymphocytes were measured during after tolerance and CLP challenge. Both subtypes of T cells Treg and Th17 analyzed showed an increase of these cells in the spleen during and after tolerance. This study demonstrated that reduced mortality after previously seen tolerance may be associated with increasing the population of regulatory T cells and Th17 because immunoregulation of the hiperinflamação and neutrophil recruitment
 
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Publishing Date
2016-09-21
 
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