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Previous issue date: 2012-04-23 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Iron is an essential element for many cellular functions, including the immune response against intracellular pathogens. In this study, we aimed evaluate the effect of iron on IRP2, IFN-?, TNF-?, IL-6, IL-10, MIG and IP10 expression in PBMC and assess the effect of the spleen parasite load on the expression of
these genes in the spleen of L. infantum naturally infected dogs. Blood sample from 7 DTH+ donor was collected and PBMC was obtained. The cells were cultivated in absence (iron chelator desferroximane, DFO 10 ?M supplemented media) or in presence of iron (hemin 6 mM) for 1 h, followed by stimulation with
Leishmania infatum antigen for 4 h. 44 dog spleen samples were obtained and parasite load in this organ was determinate by qPCR. Gene expression was analyzed by qPCR and cytokine production quantified by flow cytometry. In antigen stimulated cells, genes involved in immune response are significantly
more expressed in presence of iron. T CD4+ and TCD8+ lymphocytes produces IFN-?, TNF-? and IL-10 possibly in iron dependent pathway. Monocytes antigen stimulated reduced TNF-?, IL-6 and IL-10 production in presence of iron. We
found spleen of infected dogs IRP2 expression increases according to parasite load in that organ, while an inverse profile was found for IFN-?, TNF-? e IL-10 expression. These results suggest that T lymphocytes depends on iron to produce IFN-?, TNF-? and IL-10, while iron seems to inhibit cytokine production
in monocytes. So, we propose an immunoregulatory mechanism carried out by iron during L. infantum infection in humans and dogs / O ferro ? um elemento essencial para diversas fun??es celulares, incluindo a resposta imune a pat?genos. O objetivo deste trabalho foi avaliar o efeito do ferro sobre a express?o dos genes IRP2, IFN-?, TNF-?, IL-6, IL-10, MIG e IP10 em c?lulas mononucleares de sangue perif?rico (CMSP) humano e examinar o
efeito da carga parasit?ria espl?nica sobre a express?o destes genes no ba?o de c?es naturalmente infectados por L. infantum. Coletou-se amostras de sangue perif?rico de 7 indiv?duos DTH+ e obteve-se as CMSP. As c?lulas foram cultivadas na aus?ncia (quelante deferoxamina 10 ?M) ou presen?a de ferro
(Hemina 6 mM) por 1 hora seguido de estimula??o com ant?geno de Leishmania infantum por 4 horas. Obteve-se o ba?o de 44 c?es e determinouse a carga parasit?ria neste ?rg?o por qPCR. A express?o g?nica foi avaliada por qPCR e a produ??o de citocinas foi quantificada por citometria de fluxo. Encontramos que na presen?a de ferro a express?o de genes envolvidos na
resposta imune ? significativamente aumentada em CMSP. Linf?citos T CD4+ e TCD8+ produzem IFN-?, TNF-? e IL-10 possivelmente por uma via dependente de ferro. Em mon?citos a produ??o de TNF-?, IL-6 e IL-10 foram reduzidas em
c?lulas estimuladas e cultivadas na presen?a do metal. Foi visto que no ba?o de c?es a express?o de IRP2 aumenta de acordo com a carga parasit?ria, sendo o inverso encontrado para IFN-?, TNF-? e IL-10. Os resultados sugerem que linf?citos T dependem de ferro para produzir IFN-?, TNF-? e IL-10, enquanto em mon?citos o ferro parece ter efeito inibit?rio sobre a produ??o de
citocinas, sugerindo um efeito imunomodulat?rio para o ferro em humanos e c?es durante a leishmaniose visceral
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/12592 |
| Date | 23 April 2012 |
| Creators | Nascimento, Paulo Ricardo Porfirio do |
| Contributors | 15603016434, http://lattes.cnpq.br/7120263570947836, Medeiros, Iara Marques de, 36970360415, http://lattes.cnpq.br/0702456215392682, Carvalho, Lucas Pedreira de, 88323145504, http://lattes.cnpq.br/7308383096084856, Jer?nimo, Selma Maria Bezerra |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Bioqu?mica, UFRN, BR, Bioqu?mica; Biologia Molecular |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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