Análise genética e funcional da resposta imune na toxoplasmose ocular humana
Ano de defesa: | 2012 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Tese |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Minas Gerais
UFMG |
Programa de Pós-Graduação: |
Não Informado pela instituição
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Departamento: |
Não Informado pela instituição
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País: |
Não Informado pela instituição
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Palavras-chave em Português: | |
Link de acesso: | http://hdl.handle.net/1843/BUOS-97PFKW |
Resumo: | Toxoplasmosis is a parasitic infection that has the protozoan Toxoplasma gondii as its aetiological agent. Retinochoroiditis (RC) is the most common manifestation of toxoplasmosis in immunocompetent patients infected with the parasite. In this study, we analize the seroprevalence of toxoplasmosis in the inhabitants of Vale do Jequitinhonha. In the area, the seroprevalence of toxoplasmosis was of 43,0%. The villagers were also submitted to ophthalmological examination for the identification of toxoplasmic RC. A total of 68 cases of chronic ocular toxoplasmosis (COT) which indicates 14,4% of manifestation of ocular toxoplasmosis (TO). Based on the construction of pedigrees for the three villages, the TO multicases families were splited into trios that were analysed using a family based allelic association test (FBAT) to evaluate potential associations ith 43 polymorphisms distributed in 14 candidate genes. Among these genes, are: IL-10, IFN- and IL-12, TLR2, 4, 5 and 9, MyD88, UNC93B1, TIRAP, NOD2, P2XR7, COL2A1 and ABCA4. We found evidence of genetic association of the genes COL2A1, ABCA4, P2XR7, TLR9 and NOD2 with the development of TO. We then studied if the polymorphisms rs187084 and rs3135499, in the TLR9 and NOD2 genes and which were associated with the development of TO (p=0,042 e p=0,039, respectively) would play a role in the immune response to the parasite. Therefore, we characterized the production of citokynes and the T cell response in cases of COT and four cases of active TO (AOT) and controls. We found no differences in the production of Th1, Th2 or Th17 cytokines in patients bearing any of the possible genotypes for the rs178084 polymorphism in TLR9 gene. We also found no difference in cytokines (IFN- and IL-2) when comparing patients with AOT or COT to asymptomatic individuals. However, we found an increased production of IL-17 by PBMCs from patients with either stage of TO. The increased production of IL-17 was also associated with the heterozygous genotype on NOD2 polymorphism (rs3135499). The main source of IL-17 was shown to be CD4+/T-bet-/IFN--, Th17 lymphocytes, which were present in higher frequency in patients with scarred or active lesions of ocular toxoplasmosis. Altogether, our results suggest that NOD2 influences the production of IL17 by CD4+T helper lymphocytes, which in turn mediates the inflammatory process and might contribute to the development of ocular lesions in patients infected with T. gondii. |