Reactive Oxygen Species and Nitric Oxide in Cutaneous Leishmaniasis

Cutaneous leishmaniasis affects millions of people around the world. Several species of Leishmania infect mouse strains, and murine models closely reproduce the cutaneous lesions caused by the parasite in humans. Mouse models have enabled studies on the pathogenesis and effector mechanisms of host resistance to infection. Here, we review the role of nitric oxide (NO), reactive oxygen species (ROS), and peroxynitrite (ONOO−) in the control of parasites by macrophages, which are both the host cells and the effector cells. We also discuss the role of neutrophil-derived oxygen and nitrogen reactive species during infection with Leishmania. We emphasize the role of these cells in the outcome of leishmaniasis early after infection, before the adaptive Th-cell immune response

Safety and Immunogenicity of an In Vivo Muscle Electroporation Delivery System for DNA-hsp65 Tuberculosis Vaccine in Cynomolgus Monkeys

A Bacille Calmette–Guérin (BCG) is still the only licensed vaccine for the prevention of tuberculosis, providing limited protection against Mycobacterium tuberculosis infection in adulthood. New advances in the delivery of DNA vaccines by electroporation have been made in the past decade. We evaluated the safety and immunogenicity of the DNA-hsp65 vaccine administered by intramuscular electroporation (EP) in cynomolgus macaques. Animals received three doses of DNA-hsp65 at 30-day intervals. We demonstrated that intramuscular electroporated DNA-hsp65 vaccine immunization of cynomolgus macaques was safe, and there were no vaccine-related effects on hematological, renal, or hepatic profiles, compared to the pre-vaccination parameters. No tuberculin skin test conversion nor lung X-ray alteration was identified. Further, low and transient peripheral cellular immune response and cytokine expression were observed, primarily after the third dose of the DNA-hsp65 vaccine. Electroporated DNA-hsp65 vaccination is safe but provides limited enhancement of peripheral cellular immune responses. Preclinical vaccine trials with DNA-hsp65 delivered via EP may include a combination of plasmid cytokine adjuvant and/or protein prime–boost regimen, to help the induction of a stronger cellular immune response

The Role of GP91phox-derived reactive oxygen species in the infection caused by Leishmania amazonensis: implications relative to the site of infection

Exportado OPUSMade available in DSpace on 2019-08-14T00:39:36Z (GMT). No. of bitstreams: 1 thesis_version_final_presentation2.pdf: 12166570 bytes, checksum: 602d8285022a74666d5e6967f82ae6c5 (MD5) Previous issue date: 18As leishmanioses são um espectro de doenças causadas por parasitas do gênero Leishmania. Por ser um patógeno intracelular obrigatório, infectando principalmente macrófagos e neutrófilos, a produção de radicais de oxigênio e nitrogênio poderia ser importante fator na eliminação de parasitas. No caso específico da infecção causada por Leishmania amazonensis, uma importante espécie causadora de leishmaniose cutânea no Brasil, não há dados na literatura demonstrando o efeito desses radicais em infecções in vivo. Dados do nosso grupo confirmaram que o óxido nítrico possui um importante papel na eliminação dos parasitas em infecções causadas por L. amazonensis in vivo, porém o ânion superóxido e o peróxido de hidrogênio não parecem estar associados com a morte dos parasitas in vivo. Neste trabalho, nós mostramos que animais C57BL/6 deficientes da subunidade gp91phox da NADPH oxidase de fagócitos (gp91phox-/-) infectados de forma subcutânea com L. amazonensis desenvolvem lesões maiores nas primeiras semanas de infeção e lesões menores na fase crônica da doença quando comparados a animais selvagens (WT). Entretanto, ambos camundongos WT e gp91phox-/- apresentaram a mesma carga parasitária. Nós detectamos altos níveis de IL-17 nos linfonodos drenantes 8 semanas pós infecção (p.i.) e baixos níveis de mRNA de IL-1 no sítio da lesão 12 e 16 semanas p.i. nos camundongos gp91phox-/-. Há dados controversos na literatura sobre o papel dos neutrófilos nas infecções causadas por Leishmania principalmente quando diferentes rotas de inoculação são usadas. Considerando a relevância dessas células para produção de ROS e prevendo alterações importantes do efeito de ROS quando a rota de inoculação é alterada, nós comparamos a resposta imune inata gerada nas rotas de inoculação mais usadas no estudo da leishmaniose, as rotas subcutânea e intradérmica. Porém, usamos o modelo de infecção por L. major por este ser mais bem estabelecido na literatura. Duas horas p.i., a infecção intradérmica com L. major apresentou massivo recrutamento de neutrófilos e maiores níveis de expressão de mRNA de CXCL-1, seguido por um intenso recrutamento de monócitos inflamatórios Ly6Chi 48h e 9 dias p.i. quando comparados à infecção subcutânea. Este mais intenso perfil inflamatório observado no sítio intradérmico infectado também foi acompanhado por uma mais eficiente captura dos parasitas. Nós observamos um aumento de 10 vezes no número de células infectadas neste sítio nos tempos observados. Por outro lado, células dendríticas e macrófagos representaram a maioria das células infectadas no sítio subcutâneo. Devido à essa confirmada e importante participação de neutrófilos na infecção intradérmica, utilizamos essa rota de inoculação para determinar a influência de ROS em nosso modelo de infecção por L. amazonensis. Quando infectados de forma intradérmica com formas metacíclicas de L. amazonensis, os camundongos gp91phox-/- apresentaram lesões maiores desde 4 semanas p.i. com grande inflamação, densas áreas necróticas e perda de tecido, porém sem apresentar diferenças na carga parasitária. Curiosamente, os níveis de citocinas inflamatórias não se alteraram durante o curso de infeção, porém nós detectamos uma extensa acumulação de neutrófilos no sítio intradérmico de infecção. O elevado número de neutrófilos em camundongos gp91phox-/- foi associado com alta frequência e números de neutrófilos necróticos em 8 semanas p.i. e isso pode ser o fator principal responsável pelo fenótipo inflamatório observado nestes camundongos. Estes experimentos sugerem que radicais de oxigênio têm um importante papel desde estágios iniciais da infecção causada por L. amazonensis, controlando o fluxo de neutrófilos para o sítio da lesão, impedindo a necrose inflamatória nestas células e consequentemente a inflamação dos tecidos infectados. Além disso, a rota de inoculação influencia profundamente o efeito das espécies reativas de oxigênio (ROS) na infecção por L. amazonensis, visto que as principais células produtoras de ROS, os neutrófilos, demonstram um papel proeminente somente na infecção intradérmica. Este é o primeiro trabalho a mostrar o efeito do ROS em Leishmania em um modelo aproximado em relação à infecção natural, indicando uma via mais fisiológica para o estudo de ROS em infecções causadas por Leishmania.Leishmaniasis are a wide spectrum of diseases caused by parasites of the genus Leishmania. Because these are obligatory intracellular pathogens, infecting mainly macrophages and neutrophils, oxygen and nitrogen radicals production could be important factors in parasite killing. In the specific case of infection caused by Leishmania amazonensis, an important species causing cutaneous leishmaniasis in Brazil, there is no data in the literature demonstrating the effect of these radicals on the infection in vivo. Data from our group confirmed that nitric oxide has an important role in parasite killing in L. amazonensis infection, but superoxide and hydrogen peroxide do not appear to be associated with parasite killing in vivo. In this work, we showed that C57BL/6 mice deficient in the gp91phox subunit of NADPH-dependent oxidase of phagocytes (gp91phox-/-) infected subcutaneously with L. amazonensis develop larger lesions in the first weeks of infection and smaller lesions in the chronic phase of the disease when compared to wild type animals (WT). However, both WT and gp91phox-/- mice presented similar parasite loads. We detected higher levels of IL-17 in draining lymph nodes 8 weeks post infection (p.i.) and lower mRNA levels of IL-1 in the lesion site 12 and 16 weeks p.i. in gp91phox-/- mice. There are controversial data in the literature about the role of neutrophils in Leishmania infection, principally when different routes of inoculation are involved. Considering the relevance of these cells to ROS production and predicting important alterations of ROS effect when the inoculation route is changed, we compared the innate immune response generated on the most common used routes of parasite inoculation, the subcutaneous and the intradermal routes. However, we used the model of L. major infection, since this model is better established in the literature. Starting at 2h p.i., intradermal infection with L. major presented massive neutrophil recruitment and higher mRNA expression of CXCL-1 followed by intense recruitment of Ly6Chi inflammatory monocytes at 48h and 9 days p.i. compared to subcutaneous infection. This more intense inflammatory profile observed at the infected intradermal site also was accompanied by a more efficient parasite capture in this site. We observed a 10-fold increase in the number of infected cells at the times measured. In contrast, dendritic cells and macrophages represented the majority of infected cells in the subcutaneous site. Due this confirmed and important participation of neutrophils in the intradermal infection, we utilized this route of inoculation to determine the influence of ROS in our model of L. amazonensis infection. When infected intradermally, gp91phox-/- mice presented larger lesions starting at 4 weeks p.i. and a high degree of inflammation leading to a dense necrotic area and tissue loss without differences in parasite loads. Surprisingly, the levels of inflammatory cytokines did not change during the course of infection, but we did detect a large accumulation of neutrophils at the intradermal site. Increased neutrophil numbers in gp91phox-/- mice was associated with higher numbers and frequencies of necrotic neutrophils at 8 weeks p.i. and may be the major factor responsible for the inflammatory phenotype observed in these mice. These experiments suggest that oxygen radicals have an important role in L. amazonensis infection, controlling neutrophil flux to the lesion, impairing necrotic inflammatory death in these cells and consequently the inflammation of infected tissue. Moreover, the route of inoculation greatly influences the effect of reactive oxygen species (ROS) in L. amazonensis infection, since the major cells producing ROS, the neutrophils, play a prominent role only in intradermal infection. This is the first report to show the effect of ROS in Leishmania model closest to natural infection, indicating a more physiological way to study ROS in Leishmania infections

Evolution of anti-Trypanosoma cruzi antibody production in patients with chronic Chagas disease: correlation between antibody titers and development of cardiac disease severity

Submitted by Janaína Nascimento ([email protected]) on 2019-02-25T14:04:30Z No. of bitstreams: 1 ve_Georg_Ingebourg_etal_INI_2017.pdf: 3250239 bytes, checksum: b99e6a01f4776da5e71a3fe588b87d15 (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-02-26T14:43:08Z (GMT) No. of bitstreams: 1 ve_Georg_Ingebourg_etal_INI_2017.pdf: 3250239 bytes, checksum: b99e6a01f4776da5e71a3fe588b87d15 (MD5)Made available in DSpace on 2019-02-26T14:43:08Z (GMT). No. of bitstreams: 1 ve_Georg_Ingebourg_etal_INI_2017.pdf: 3250239 bytes, checksum: b99e6a01f4776da5e71a3fe588b87d15 (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Setor de Imunodiagnóstico. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Doença de Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Doença de Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Doença de Chagas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Chagas disease is one of the most important endemic infections in Latin America affecting around 6-7 million people. About 30-50% of patients develop the cardiac form of the disease, which can lead to severe cardiac dysfunction and death. In this scenario, the identification of immunological markers of disease progression would be a valuable tool for early treatment and reduction of death rates. In this observational study, the production of anti-Trypanosoma cruzi antibodies through a retrospective longitudinal follow-up in chronic Chagas disease patients´ cohort and its correlation with disease progression and heart commitment was evaluated. Strong inverse correlation (ρ = -0.6375, p = 0.0005) between anti-T. cruzi IgG1 titers and left ventricular ejection fraction (LVEF) in chronic Chagas cardiomyopathy (CCC) patients were observed after disease progression. Elevated levels of anti-T. cruzi IgG3 titers were detected in all T. cruzi-infected patients, indicating a lack of correlation of this IgG isotype with disease progression. Furthermore, low levels of anti-T. cruzi IgG2, IgG4, and IgA were detected in all patients through the follow-up. Although without statistical significance anti-T. cruzi IgE tends to be more reactive in patients with the indeterminate form (IND) of the disease (p = 0.0637). As this study was conducted in patients with many years of chronic disease no anti-T. cruzi IgM was detected. Taken together, these results indicate that the levels of anti-T. cruzi IgG1 could be considered to seek for promising biomarkers to predict the severity of chronic Chagas disease cardiomyopathy

Putative role of HLA polymorphism among a Brazilian HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) population

Abstract Around ten million people are infected with HTLV-1 worldwide, and 1–4% develop HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), characterized by an important degeneration of the spinal cord, which can lead to death. Distinct HLA alleles have been associated with either HAM/TSP susceptibility or protection. However, these HLA alleles set may change according to the population studied. Brazil is the second country in the number of HTLV-1-infected people and there are few reports addressing the HLA influence on HTLV-1 infection as well as on disease outcome. The objective of this study was to evaluate the influence of HLA alleles as a risk factor for HAM/TSP and the proviral load (PVL) levels, clinical progression, and death outcomes in an admixed Brazilian population. The HLA-A, -B, -C, and -DRB1 were genotyped in 375 unrelated HTLV-1-infected individuals divided into asymptomatic carriers (AC) (n = 165) and HAM/TSP (n = 210) in a longitudinal cohort from 8 to 22 years of follow-up. Because locus B deviated from Hardy–Weinberg Equilibrium for the study groups, the results represented for HLA-B alleles were inconclusive. The alleles HLA-A*68 and -C*07 were related to HAM/TSP risk in multivariate analysis. The alleles HLA-A*33, and -A*36 were associated with protection against disease progression in HAM/TSP patients, while -C*12, -C*14, and -DRB1*08 were associated with increased risk of death. In the AC group, the presence of, -C*06 and -DRB1*15 alleles influenced an increased PVL, in an adjusted linear regression model, while -A*30, -A*34, -C*06, -C*17 and -DRB1*09 alleles were associated with increased PVL in HAM/TSP group compared to HAM/TSP individuals not carrying these alleles. All these alleles were also related to increased PVL associated with clinical progression outcome. Increased PVL associated with the death outcome was linked to the presence of HLA-A*30. PVL has been associated with HLA, and several alleles were related in AC and HAM/TSP patients with or without interacting with clinical progression outcomes. Understanding the prognostic value of HLA in HAM/TSP pathogenesis can provide important biomarkers tools to improve clinical management and contribute to the discovery of new therapeutic interventions

Site-dependent recruitment of inflammatory cells determines the effective dose of leishmania major

Submitted by Rodrigo Senorans ([email protected]) on 2015-06-17T18:13:19Z No. of bitstreams: 1 Site-Dependent Recruitment of Inflammatory Cells Determines the.pdf: 4547942 bytes, checksum: a0c07295ddd9aca2f1ca951279b7bebb (MD5)Approved for entry into archive by Anderson Silva ([email protected]) on 2015-06-18T14:15:53Z (GMT) No. of bitstreams: 1 Site-Dependent Recruitment of Inflammatory Cells Determines the.pdf: 4547942 bytes, checksum: a0c07295ddd9aca2f1ca951279b7bebb (MD5)Approved for entry into archive by Anderson Silva ([email protected]) on 2015-06-18T14:16:40Z (GMT) No. of bitstreams: 1 Site-Dependent Recruitment of Inflammatory Cells Determines the.pdf: 4547942 bytes, checksum: a0c07295ddd9aca2f1ca951279b7bebb (MD5)Made available in DSpace on 2015-06-18T18:35:21Z (GMT). No. of bitstreams: 1 Site-Dependent Recruitment of Inflammatory Cells Determines the.pdf: 4547942 bytes, checksum: a0c07295ddd9aca2f1ca951279b7bebb (MD5) Previous issue date: 2014NIH-CAPESNational Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil / National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Laboratório de Gnotobiologia e Imunologia. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA / Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Laboratório de Gnotobiologia e Imunologia. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA.National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA.National Institute of Allergy and Infectious Diseases. Laboratory of Parasitic Diseases. Bethesda, MD, USA.The route of pathogen inoculation by needle has been shown to influence the outcome of infection. Employing needle inoculation of the obligately intracellular parasite Leishmania major, which is transmitted in nature following intradermal (i.d.) deposition of parasites by the bite of an infected sand fly, we identified differences in the preexisting and acute cellular responses in mice following i.d. inoculation of the ear, subcutaneous (s.c.) inoculation of the footpad, or inoculation of the peritoneal cavity (intraperitoneal [i.p.] inoculation). Initiation of infection at different sites was associated with different phagocytic populations. Neutrophils were the dominant infected cells following i.d., but not s.c. or i.p., inoculation. Inoculation of the ear dermis resulted in higher frequencies of total and infected neutrophils than inoculation of the footpad, and these higher frequencies were associated with a 10-fold increase in early parasite loads. Following inoculation of the ear in the absence of neutrophils, parasite phagocytosis by other cell types did not increase, and fewer parasites were able to establish infection. The frequency of infected neutrophils within the total infected CD11b+ population was higher than the frequency of total neutrophils within the total CD11b+ population, demonstrating that neutrophils are overrepresented as a proportion of infected cells. Employing i.d. inoculation to model sand fly transmission of parasites has significant consequences for infection outcome relative to that of s.c. or i.p. inoculation, including the phenotype of infected cells and the number of parasites that establish infection. Vector-borne infections initiated in the dermis likely involve adaptations to this unique microenvironment. Bypassing or altering this initial step has significant consequences for infection

TNFR1 single nucleotide polymorphisms are not associated with cervical HPV-induced pre-malignant lesion but regulate in situ cervical TNFR1 expression

Submitted by Janaína Nascimento ([email protected]) on 2019-03-19T14:24:44Z No. of bitstreams: 1 ve_Rocha_Natália_etal_INI_2019.pdf: 3415620 bytes, checksum: dcec2b0d13083210cf995db8672638bd (MD5)Approved for entry into archive by Janaína Nascimento ([email protected]) on 2019-03-22T19:36:22Z (GMT) No. of bitstreams: 1 ve_Rocha_Natália_etal_INI_2019.pdf: 3415620 bytes, checksum: dcec2b0d13083210cf995db8672638bd (MD5)Made available in DSpace on 2019-03-22T19:36:22Z (GMT). No. of bitstreams: 1 ve_Rocha_Natália_etal_INI_2019.pdf: 3415620 bytes, checksum: dcec2b0d13083210cf995db8672638bd (MD5) Previous issue date: 2019Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Laboratório de Anatomia Patológica. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.State University of Rio de Janeiro. Department of Biochemistry. Rio de Janeiro, RJ, Brazil.State University of Rio de Janeiro. Department of Rheumatology. Rio de Janeiro, RJ, Brazil.State University of Rio de Janeiro. Department of Biochemistry. Rio de Janeiro, RJ, Brazil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Imunologia e Imunogenética em Doenças Infecciosas. Rio de Janeiro, RJ, Brasil.TNF-α is involved in HPV infection control by triggering cell signaling through binding in specific receptors TNFR1 and TNFR2. Genetic polymorphisms in these receptors may influence TNF-α signaling. Herein, we investigated TNFR1 rs767455 andrs2234649 single nucleotide polymorphisms, and TNFR1 protein expression in cervical squamous intraepithelial lesions (SIL) to identify their role in cervical pre-malignant development. SIL patients (n = 179) and healthy volunteers (n = 227) were enrolled for TNFR1 genotyping analysis by PCR-RFLP in blood samples and TNFR1 protein expression in cervical tissue by immunohistochemistry. No statistical differences regard genotypes and allelic frequencies for both polymorphisms were observed. Cervical TNFR1-expressing cells were rare in epithelium and basal layer regardless the groups. However, a progressive increase in infiltrating cells was observed in the stromal area, mainly in high SIL (HSIL) group compared to low SIL (LSIL, p <0.001) and control (p < 0.001) groups. TNFR1-expressing cells frequency was higher in TNFR1 rs767455AG/GG (p < 0.001), and in rs2234649AA (p < 0.001) genotypes carries in HSIL subgroup. These data indicated that TNFR1-expression is abrogated in cervical epithelium, where HPV-induced pre-malignant lesion occurs, increasing its frequency in inflammatory cells in stroma, and is genetically controlled by TNFR1 rs767455AG/GG and rs234649AA genotypes. These biomarkers may be useful to identify cervical precancerous lesions progression

Lack of association between single-nucleotide polymorphisms of pro- and anti-inflammatory cytokines and HTLV-1-associated myelopathy / tropical spastic paraparesis development in patients from Rio de Janeiro, Brazil

Abstract Background HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive neurological and inflammatory disease, associated with HTLV-1 infection. HAM/TSP neurological disease is a consequence of an inflammatory reaction, and adaptive immune responses, through the secretion of anti-inflammatory and pro-inflammatory cytokines, play an important role in the outcome of infection and disease progression. Studies addressing the association between cytokines functional single nucleotide polymorphisms and HAM/TSP development are scarce. Methods The genetic polymorphisms of cytokine genes were evaluated in HAM/TSP patients (n = 68) and in asymptomatic HTLV-1 positive carriers (n = 83) from Rio de Janeiro, Brazil, in a case-control study. HTLV-1 infected patients were genotyped for SNPs in five cytokine genes: TNFA-308G/A, IL6-174G/C, IFNG + 874 T/A, TGFB at the codons + 10 T/C and + 25G/C, IL10-592C/A and -819C/T, and -1082A/G and proviral load (PVL) was quantified. Associations between genotypes, haplotypes, clinical outcome and pro viral load were evaluated. Results Lack of association between the cytokine polymorphisms and disease outcome was observed. The genotypes TNFA-308GG, IL6-174GG/GC, IL10-592AA and -819CC and TGFb1 high producers phenotypes were correlated with higher PVL in HAM/TSP patients versus asymptomatic carriers. Conclusions We did not observe association between cytokine polymorphisms and risk for HAM/TSP development in Brazilian HTLV-1 infected individuals, regardless of differences in PVL between HAM/TSP versus asymptomatic carriers in specific cytokine polymorphisms

IgE reactivity to <i>T</i>. <i>cruzi</i> antigen.

<p>IgE reactivity to <i>T</i>. <i>cruzi</i> antigen.</p