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Influence of extra and intracellular flagellin recognition in the regulation of macrophage pyroptosis.

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Author(s):
Silvia Lucena Lage
Total Authors: 1
Document type: Master's Dissertation
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI)
Defense date:
Examining board members:
Karina Ramalho Bortoluci; Niels Olsen Saraiva Câmara; Soraya Soubhi Smaili
Advisor: Karina Ramalho Bortoluci
Abstract

Flagellin is recognized by TLR5, and NLRs NLRC4/Naip5. The latter induce activation of caspase-1 and release of IL-1b and IL-18, besides the death of macrophages by pyroptosis. To investigate the molecular mechanisms involved in these processes, peritoneal MOs were stimulated with flagellin from B. subtilis and S. typhimurium in its free form (activating TLR5), or inserted into lipid vesicles (able to activate NLRs). We demonstrated that both cytosolic flagellins induce the production of IL-1b and cell death, while the flagellin of S. typhimurium has shown greater potential to induce production of IL-1b and IL-6 by MOs. We found that the production of IL-1b and cell lysis by MOs are subsequent events proven by the formation of pores in cell membranes. Although the release of IL-1b after recognition of both flagellins is a phenomenon dependent on the axis NLRC4/caspase-1, cell death induced by cytosolic flagellin occurs in the absence of these molecules, unlike that provided by the current literature. (AU)

FAPESP's process: 09/03644-0 - Influence of extra and intracellular flagellin recognition in the regulation of macrophage pyroptosis and autophagy.
Grantee:Silvia Lucena Lage
Support Opportunities: Scholarships in Brazil - Master