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Master's Dissertation
DOI
10.11606/D.42.2010.tde-11082010-142224
Document
Author
Full name
Julia Cortina Campopiano
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2010
Supervisor
Committee
Mendes, Joao Gustavo Pessini Amarante (President)
Boscardin, Silvia Beatriz
Lopes, Marcela de Freitas
Title in Portuguese
Influência da ativação de macrófagos via receptores do tipo Toll (TLRs) na produção de fatores moduladores da sobrevivência de linfócitos T.
Keywords in Portuguese
Apoptose
Fas/FasL
Linfócitos T
Macrófagos
PAMPs
Receptores do tipo Toll (TLRs)
Abstract in Portuguese
A interação entre a imunidade inata e adaptativa acontece durante diversas fases da resposta imune. Os Toll-like receptors (TLRs) tem importante papel na ativação de macrófagos e portanto, no conjunto de moléculas secretadas por estas células. Pouco se sabe sobre o papel destas substâncias no processo de contração da população de células T ativadas (Activation-induced cell death - AICD). Portanto, o objetivo do presente trabalho foi avaliar se macrófagos estimulados com diferentes agonistas de TLRs poderiam produzir fatores solúveis com capacidade modulatória da morte por AICD. Primeiramente, demonstramos que tanto a linhagem macrofágica J774, quanto os macrófagos derivados de medula óssea (BMDMs) expressam todos os TLRs, com excessão do TLR11. Comprovamos que estas proteínas são funcionais, uma vez que o estímulo com agonistas de TLRs leva à ativação de NF-κB nestes macrófagos. Finalmente, mostramos que os sobrenadantes gerados pelos macrófagos são capazes de proteger as células DO11.10 da AICD, via a regulação negativa de FasL, parcialmente mediada por PGE2.
Title in English
Effect of soluble factors produced by TLR-activated macrophages on T lymphocytes survival.
Keywords in English
Toll-like receptors (TLRs)
Apoptosis
Fas/FasL
Macrophages
PAMPs
T lymphocyte
Abstract in English
The interaction between innate and adaptative immunity occurs in several phases of the immune response. The Toll-like receptors (TLRs) have an important role in the activation of macrophages directly acting on the molecules secreted by these cells. Little is known about the role of these secreted molecules on the survival control of activated T lymphocytes (Activation-induced cell death - AICD). Therefore, the objective of the present work was to evaluate the effects of soluble factors produced by macrophages activated with several TLRs agonists, on the survival of T lymphocytes. First we sought the expression of TRLs on both bone marrow-derived and J774 macrophage cell line and we could see that both cells express all TLRs, except for TLR 11. The stimulation of both cells with TLRs agonists leads to the expression of NF-κB and the production of soluble factors that are able to protect DO11.10 T lymphocyte cell line from AICD, via down regulation of FasL partially mediated by PGE2.
 
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Publishing Date
2010-09-15
 
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