• JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
  • JoomlaWorks Simple Image Rotator
 
  Bookmark and Share
 
 
Master's Dissertation
DOI
https://doi.org/10.11606/D.17.2020.tde-07042021-145431
Document
Author
Full name
Valter Vinícius Silva Monteiro
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2020
Supervisor
Committee
Cunha, Fernando de Queiroz (President)
Cunha, Larissa Dias da
Salomão, Reinaldo
Title in Portuguese
O papel do STING na imunopatologia da sepse
Keywords in Portuguese
Ácidos nucleicos extracelulares
AIM2
DNA extracelular
PRR
Sepse
STING
TLR9
Abstract in Portuguese
A sepse é uma síndrome complexa causada pela resposta imune desregulada desencadeada por uma infecção, levando a disfunção de órgãos. Uma característica comum descrita na sepse é a presença de altos níveis de DNA circulante (cfDNA) no plasma desses pacientes. Nesse sentido, foi demonstrado que existe uma correlação positiva entre os níveis de DNA e a mortalidade de pacientes com sepse. Portando, faz-se necessário uma melhor investigação acerca dos mecanismos através dos quais o DNA extracelular contribui para fisiopatologia da sepse. Com base nisso, o objetivo deste estudo é investigar as características dos cfDNA e seu papel na patogênese da sepse. Nesse sentido, utilizamos o modelo de CLP em camundongos deficientes deTLR9, STING e AIM2 para avaliar o papel de cada receptor no prognóstico da sepse. Observamos que o receptor de DNA, STING, está envolvido na produção de NETs durante a sepse. A estimulação de neutrófilos com DNA é capaz de induzir a produção de NETs in vitro e quando utilizados camundongos deficientes para o receptor STING, animais submetidos ao modelo de sepse letal possuem uma maior sobrevida e uma menor carga bacteriana. Além disso, esse animais possuem uma menor produção de NETs, citocinas e lesão de órgãos. Deste modo, podemos concluir que o STING está envovido na patogenese da sepse induzindo a produção de NETs.
Title in English
The role of STING in the sepsis immunopathology
Keywords in English
AIM2
Cell-free DNA
Cell-free Nucleic acids
PRR
Sepsis
STING
TLR9
Abstract in English
Sepsis is a syndrome caused by the unregulated immune response triggered by an infection, leading to organ dysfunction. A common feature described in sepsis is the presence of high levels of circulating cell-free DNA (cfDNA) in the plasma of these patients. In this sense, it has been shown that there is a positive correlation between DNA levels in the plasma and mortality in patients with sepsis. Therefore, a better investigation about the mechanisms through which extracellular DNA contributes to the pathophysiology of sepsis is necessary. Based on this, the aim of this study is to investigate the characteristics of cfDNA and its role in the pathogenesis of sepsis. In this sense, we used the PLC model in TLR9, STING and AIM2 deficient mice to assess the role of each receptor in the prognosis of sepsis. We observed that the DNA receptor, STING, is involved in the production of NETs during sepsis. Stimulation of neutrophils with DNA is able to induce the production of NETs in vitro and when mice deficient for the STING receptor, animals submitted to the lethal sepsis model have a longer survival and a lower bacterial load. In addition, these animals have a lower production of NETs, cytokines and organ damage. Thus, we can conclude that STING is involved in the pathogenesis of sepsis, inducing the production of NETs.
 
WARNING - Viewing this document is conditioned on your acceptance of the following terms of use:
This document is only for private use for research and teaching activities. Reproduction for commercial use is forbidden. This rights cover the whole data about this document as well as its contents. Any uses or copies of this document in whole or in part must include the author's name.
Publishing Date
2021-04-19
 
WARNING: Learn what derived works are clicking here.
All rights of the thesis/dissertation are from the authors
CeTI-SC/STI
Digital Library of Theses and Dissertations of USP. Copyright © 2001-2022. All rights reserved.