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Role of inflammasomes in dendritic cell maturation and induction of adaptive responses.

Grant number: 11/12639-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): November 01, 2011
Effective date (End): July 31, 2014
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Karina Ramalho Bortoluci
Grantee:Thaís Boccia da Costa
Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:08/50958-8 - Interaction between innate immune receptors in the activation of macrophages and dendritic cells, AP.JP


Microbial pathogens are recognized through multiple, distinct PRRs that can be broadly categorized into secreted, transmembrane, and cytosolic classes. The transmembrane PRRs include the Toll-like receptor (TLR) family and the C-type lectins. TLRs in mammals are either expressed on the plasma membrane or in endosomal/lysosomal organelles. The cytosolic PRRs include the retinoic acid- inducible gene I (RIG-I)-like receptors (RLRs) and the nucleotide-binding domain and leucine rich repeat-containing receptors (NLRs). The activation of the immune innate system by TLRs is able to induce the maturation of dendritic cells (DCs) and induce the production of pro-inflammatory cytokines generating favorable conditions for naïve T-cell activation. Although different in signaling processes, TLRs and NLRs seem to share ligands, such as flagellin. Flagellin is the principal component of bacterial flagellum, and is present in large amounts on nearly all flagellated bacteria such as Salmonella typhimurium. This protein is recognized by the innate immune system by TLR5 and by NLRs Naip5 and IPAF, when found in the cytosol. Recognition of flagellin by NLRs leads to the formation of a structure called inflammasome which is responsible for the activation of caspase-1 and production of pro-inflammatory cytokines such as IL-1 and IL-18 in their active forms. The effects of flagellin in the adaptive immunity have been described and its ability to activate DCs and induce proliferation of T lymphocytes. The the redundant role of TLR5 and IPAF in flagellin-induced antibody production has been shown, however in mice deficient for both receptors, antibody production is abolished. Besides, the role of these receptors in activation and proliferation of T lymphocytes still needs to be investigated. Thus, our main goal is to investigate the role of flagellin recognition by TRL5 and IPAF in DCs maturation and the induction of adaptive immune responses.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
COSTA, Thaís Boccia da. Role of inflammasome activation in the maturation of dendritic cells and in the development of adaptive imune response.. 2014. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.

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