RESUMO
Ocular toxoplasmosis is a retinitis -almost always accompanied by vitritis and choroiditis- caused by intraocular infection with Toxoplasma gondii. Depending on retinal location, this condition may cause substantial vision impairment. T. gondii is an obligate intracellular protozoan parasite, with both sexual and asexual life cycles, and infection is typically contracted orally by consuming encysted bradyzoites in undercooked meat, or oocysts on unwashed garden produce or in contaminated water. Presently available anti-parasitic drugs cannot eliminate T. gondii from the body. In vitro studies using T. gondii tachyzoites, and human retinal cells and tissue have provided important insights into the pathogenesis of ocular toxoplasmosis. T. gondii may cross the vascular endothelium to access human retina by at least three routes: in leukocyte taxis; as a transmigrating tachyzoite; and after infecting endothelial cells. The parasite is capable of navigating the human neuroretina, gaining access to a range of cell populations. Retinal Müller glial cells are preferred initial host cells. T. gondii infection of the retinal pigment epithelial cells alters the secretion of growth factors and induces proliferation of adjacent uninfected epithelial cells. This increases susceptibility of the cells to parasite infection, and may be the basis of the characteristic hyperpigmented toxoplasmic retinal lesion. Infected epithelial cells also generate a vigorous immunologic response, and influence the activity of leukocytes that infiltrate the retina. A range of T. gondii genotypes are associated with human ocular toxoplasmosis, and individual immunogenetics -including polymorphisms in genes encoding innate immune receptors, human leukocyte antigens and cytokines- impacts the clinical manifestations. Research into basic pathogenic mechanisms of ocular toxoplasmosis highlights the importance of prevention and suggests new biological drug targets for established disease.
Assuntos
Toxoplasmose Ocular/etiologia , Animais , Coriorretinite/diagnóstico , Coriorretinite/parasitologia , Coriorretinite/terapia , Infecções Oculares Parasitárias/diagnóstico , Infecções Oculares Parasitárias/parasitologia , Infecções Oculares Parasitárias/terapia , Humanos , Toxoplasma/patogenicidade , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/terapiaRESUMO
Toxoplasma gondii infection is an important cause of infectious ocular disease. The physiopathology of retinochoroidal lesions associated with this infection is not completely understood. The present study was undertaken to investigate cytokine production by T cells from individuals with active toxoplasmic retinochoroiditis (TR) comparing with controls. Eighteen patients with active TR and 15 healthy controls (6 controls IgG+ to Toxoplasma and 9 negative controls) were included in the study. Peripheral blood mononuclear cells were incubated in the presence or absence of T. gondii antigen (STAg), and stained against CD4, CD8, TNF, IL-10 and IFN-γ. Baseline expression of cytokines was higher in TR/IgG+ patients in comparison with controls. Cytokine expression was not increased by STAg in vitro stimulation in controls. After stimulation, TR/IgG+ patients' lymphocytes increased cytokine as compared to cultures from both controls. While T cells were the main source of IL-10, but also IFN-γ and TNF, other lymphocyte populations were relevant source of inflammatory cytokines. Interestingly, it was observed a negative correlation between ocular lesion size and IL-10 expression by CD4+ lymphocytes. This study showed that T cells are the main lymphocyte populations expressing IL-10 in patients with TR. Moreover, expression of IL-10 plays a protective role in active TR.
Assuntos
Imunomodulação , Linfócitos T/imunologia , Toxoplasma/imunologia , Toxoplasmose Ocular/imunologia , Toxoplasmose Ocular/parasitologia , Adolescente , Adulto , Anticorpos Anti-Helmínticos/imunologia , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Humanos , Imunoglobulina G/imunologia , Mediadores da Inflamação , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T/metabolismo , Toxoplasmose Ocular/diagnóstico , Toxoplasmose Ocular/metabolismo , Adulto JovemRESUMO
PURPOSE: Experimental data have demonstrated a relevant role for IL-6 in the modulation of acute ocular toxoplasmosis. Therefore, we aim to investigate the possible association between the IL-6 gene polymorphism at position -174 and toxoplasmic retinochoroiditis (TR) in humans. METHODS: Ninety-seven patients with diagnosed TR were recruited from the Uveitis Section, Federal University of Minas Gerais. For comparison, 83 healthy blood donors with positive serology for toxoplasmosis and without retinal signs of previous TR were included in the study. Genomic DNA was obtained from oral swabs of individuals and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus -174 of IL-6 (-174G/C). PCR products were submitted to restriction endonuclease digestion and analysed by polyacrylamide gel electrophoresis to distinguish allele G and C of the IL-6 gene, allowing the detection of the polymorphism and determination of genotypes. RESULTS: There was a significant difference in the genotype (χ(2) = 12.9, p = 0.001) and allele (χ(2) = 6.62, p = 0.01) distribution between TR patients and control subjects. In a subgroup analysis, there was no significant difference in genotypes and allele frequencies regarding TR recurrence. CONCLUSIONS: This study suggests that the genotypes related with a lower production of IL-6 may be associated with the occurrence of TR.
Assuntos
Coriorretinite/genética , DNA/genética , Interleucina-6/genética , Polimorfismo Genético , Toxoplasmose Ocular/genética , Adulto , Alelos , Animais , Coriorretinite/metabolismo , Coriorretinite/parasitologia , Eletroforese em Gel de Poliacrilamida , Feminino , Seguimentos , Frequência do Gene , Genótipo , Humanos , Interleucina-6/metabolismo , Masculino , Reação em Cadeia da Polimerase , Toxoplasmose Ocular/metabolismo , Toxoplasmose Ocular/parasitologiaRESUMO
PURPOSE: It has been proposed that cytokine gene polymorphisms can predispose individuals to disease by enhancing inflammatory processes. Considering the relevance of interleukin-1 (IL-1) in the pathogenesis of toxoplasmic retinochoroiditis (TR), we investigated whether IL1A -889 C/T and IL1B +3954C/T promoter polymorphisms are associated with TR in humans. METHODS: We performed a cross-sectional study that involved 100 Brazilian TR patients and 100 age- and gender-matched control subjects. Genomic DNA was obtained from oral swabs of all participants and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus -889 of IL1A and +3954 of IL1B. PCR products were submitted to digestion and analyzed by PAGE to distinguish C and T alleles. RESULTS: There was no significant difference in the genotype or allele distributions of the IL1A -889 C/T and IL1B +3954C/T polymorphisms in patients with TR when compared with controls. However, in a subgroup analysis, the frequency of genotype and allele distributions of IL1A -889 C/T differed significantly between TR patients with and without recurrent episodes. CONCLUSION: This study suggests that the genotypes related with a high production of IL-1a may be associated with the recurrence of TR.
Assuntos
Coriorretinite/complicações , Coriorretinite/genética , Interleucina-1alfa/genética , Interleucina-1beta/genética , Polimorfismo Genético , Toxoplasmose Ocular/complicações , Toxoplasmose Ocular/genética , Alelos , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , MasculinoRESUMO
PURPOSE: Experimental data have demonstrated a relevant role for IL-10, an anti-inflammatory cytokine, in the modulation of acute ocular toxoplasmosis. Therefore, this study was conducted to investigate the possible association between an IL10 gene polymorphism at position -1082 and toxoplasmic retinochoroiditis (TR) in humans. METHODS: One hundred patients with diagnosed TR were recruited from the Uveitis Section, Federal University of Minas Gerais. For comparison, one hundred healthy blood donors with positive serology for toxoplasmosis and without retinal signs of previous TR were included in the study. Genomic DNA was obtained from oral swabs of individuals and amplified using polymerase chain reaction (PCR) with specific primers flanking the locus -1082 of IL10 (-1082G/A). PCR products were subjected to restriction endonuclease digestion and analyzed by polyacrylamide gel electrophoresis, to distinguish allele G and A of the IL-10 gene, allowing the detection of the polymorphism and determination of genotypes. RESULTS: There was a significant difference in the genotype distribution between TR patients and control subjects (chi(2) = 6.33, P = 0.04). Carriers of the IL10 -1082 A allele (AA+AG genotypes) were more often patients with TR than control subjects (chi(2) = 5.97, P = 0.01, OR, 2.55; 95% CI, 1.11 < OR < 5.55). In a subgroup analysis, there was no significant difference in genotypes and allele carriage regarding visual acuity, involvement of both eyes and TR recurrence. CONCLUSIONS: This study suggests that the genotypes related with a low production of IL-10 may be associated with the occurrence of TR.