RESUMO
Approximately 5% of people infected with human T lymphotropic virus type 1 (HTLV-1) develop clinical myelopathy or tropical spastic paraparesis (HAM/TSP) that is associated with high-levels of Th1 cytokines, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. Chemokines are known to induce cytokine secretion and direct the trafficking of immune cells to sites of disease. The present study measured serum chemokines correlated with autonomously released IFN-gamma in cell cultures. HTLV-1 infection was defined by enzyme-linked immunosorbent assay (ELISA) and confirmed by Western blot. Subjects included HTLV-1 carriers (n = 56), patients with HAM/TSP (n = 31) and healthy HTLV-1 seronegative volunteer controls (n = 20). Serum chemokines and IFN-gamma autonomously released by mononuclear cells in culture were quantified by ELISA. Compared to HTLV-1 carriers, serum chemokines in HAM/TSP patients showed significantly increased levels of CXCL9 and CXCL10, significantly diminished levels of CCL2 and similar amounts of CCL11 and CCL24. In contrast, CCL11 and CCL24 were significantly lower in serum of HAM/TSP patients than either control. IFN-gamma was positively correlated with CXCL9 and CXCL10 when HAM/TSP and HTLV-1 carriers were used as a combined group. However, despite a large proportion of HTLV-1 carriers having high IFN-gamma levels, these chemokines were not increased in carriers. This study showed that high levels of CXCL9 and CXCL10 in the systemic circulation and low serum CCL2 levels are features of HAM/TSP. HTLV-1 infection and Tax and/or additional viral encoded factor-mediated pathological processes triggering T cell activation with autogenous IFN-gamma release are probably involved in regulating chemokine release.
Assuntos
Quimiocinas/sangue , Vírus Linfotrópico T Tipo 1 Humano , Paraparesia Espástica Tropical/diagnóstico , Biomarcadores/sangue , Portador Sadio/diagnóstico , Portador Sadio/imunologia , Estudos de Casos e Controles , Quimiocina CCL11 , Quimiocina CCL2/sangue , Quimiocina CCL24 , Quimiocina CXCL10 , Quimiocina CXCL9 , Quimiocinas CC/sangue , Quimiocinas CXC/sangue , Diagnóstico Diferencial , Ensaio de Imunoadsorção Enzimática , Humanos , Interferon gama/sangue , Interleucina-8 , Paraparesia Espástica Tropical/imunologia , Estatísticas não ParamétricasRESUMO
The immunological response in HTLV-1 infected individuals is characterized by a prominent Type-1 cytokine response with high production of IFN-gamma and TNF-alpha. In contrast, helminthic infections and in particular chronic schistosomiasis are associated with a predominant production of IL-4, IL-5, IL-10 and IL-13. Liver fibrosis is the main pathological finding in schistosomiasis that occurs after many years of infection. This pathology is T cell dependent but the immune response mechanisms are not completely understood. The North-east region of Brazil is endemic for both HTLV-1 and schistosomiasis. In the present study the immune response, clinical severity, and therapeutic response to praziquantel of patients with schistosomiasis coinfected with HTLV-1 were compared with patients infected only with S. mansoni. Patients with HTLV-1 and S. mansoni had lower levels of IL-5 (P < 0.05) and higher levels of IFN-gamma (P < 0.05) in cultures stimulated with S. mansoni antigen and decreased S. mansoni antigen specific IgE levels when compared with patients with schistosomiasis without HTLV-1 coinfection. Liver fibrosis was mild in all HTLV-1 coinfected patients and efficacy of praziquantel was lower in patients dually infected than in patients infected only with S. mansoni.
Assuntos
Infecções por HTLV-I/complicações , Esquistossomose mansoni/complicações , Adulto , Animais , Anti-Helmínticos/uso terapêutico , Antígenos de Helmintos/imunologia , Células Cultivadas , Feminino , Infecções por HTLV-I/imunologia , Humanos , Imunoglobulina E/biossíntese , Interferon gama/biossíntese , Interleucina-5/biossíntese , Cirrose Hepática/parasitologia , Masculino , Pessoa de Meia-Idade , Praziquantel/uso terapêutico , Schistosoma mansoni/imunologia , Esquistossomose mansoni/tratamento farmacológico , Esquistossomose mansoni/imunologia , Resultado do Tratamento , Fator de Necrose Tumoral alfa/biossínteseRESUMO
The aim of this study was to determine whether human T-cell lymphocytotropic virus type 1 (HTLV-1) infection may affect the levels of parasite-specific immunoglobulin (Ig) G and IgE and the positivity of the skin test for strongyloidiasis. Participants included 67 patients with strongyloidiasis (40 without HTLV-1 infection and 27 coinfected with HTLV-1). We determined IgG and IgE levels by enzyme-linked immunosorbent assay, and the immediate hypersensitivity skin test was performed with the metabolic Strongyloides stercoralis antigen. Specific IgE levels and the size of skin reactions in patients without HTLV-1 were higher (P < 0.01) than those observed in patients coinfected with HTLV-1. Additionally, 89% of patients without HTLV-1 had specific IgE and 92.5% had positive skin tests; however, these values were significantly reduced (P < 0.01) in patients coinfected with HTLV-1 (44% and 59%, respectively). These data show that HTLV-1 infection decreases the sensitivity of detection of S. stercoralis-specific IgE, the size of the immediate hypersensitivity reaction, and the sensitivity of these tests in the diagnosis of strongyloidiasis.
Assuntos
Infecções por HTLV-I/imunologia , Estrongiloidíase/diagnóstico , Adulto , Anticorpos Anti-Helmínticos/sangue , Feminino , Humanos , Imunoglobulina E/sangue , Imunoglobulina G/sangue , Masculino , Sensibilidade e Especificidade , Testes Sorológicos , Testes CutâneosRESUMO
Eosinophils, immunoglobulin (Ig)E and cytokines have important roles in defence mechanisms against helminths. In this study, the influence of HTLV-1 infection, characterized by a Th1 type of immune response, was evaluated on the cytokine pattern and parasitic specific IgE response in patients with strongyloidiasis. Patients were divided into four groups: strongyloidiasis without HTLV-1 infection, strongyloidiasis with HTLV-1, HTLV-1 without strongyloidiasis and controls without either helminth infection or HTLV-1. The cytokine profile was determined in supernatants of mononuclear cells stimulated with Strongyloides stercoralis crude antigen and the parasite specific IgE was measured by ELISA. Patients coinfected with HTLV-1 had higher levels of interferon (IFN)-gamma and interleukin (IL)-10 (P < 0.05) and lower levels of IL-5 and IgE (P < 0.05) than patients with strongyloidiasis without HTLV-1. There was an inverse relationship between IFN-gamma and IL-5 (P = 0.01; rs = - 0.37) and between IFN-gamma and parasite specific IgE (P = 0.01; rs = - 0.39), and a direct relationship between IFN-gamma and IL-10 (P = 0.04; rs = 0.35). These data show that coinfection with HTLV-1 decreases IL-5 and IgE responses in patients with strongyloidiasis consistent with a relative switch from Th2 to Th1 response. Immunological responses such as these are important in the control of this helminthic infection.
Assuntos
Citocinas/sangue , Infecções por HTLV-I/imunologia , Strongyloides stercoralis/imunologia , Estrongiloidíase/imunologia , Células Th2/imunologia , Adulto , Animais , Anticorpos Anti-Helmínticos/sangue , Células Cultivadas , Citocinas/biossíntese , Infecções por HTLV-I/sangue , Infecções por HTLV-I/complicações , Vírus Linfotrópico T Tipo 1 Humano/imunologia , Humanos , Imunoglobulina E/sangue , Interferon gama/sangue , Interleucina-10/sangue , Interleucina-13/sangue , Interleucina-5/sangue , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/imunologia , Estrongiloidíase/sangue , Estrongiloidíase/complicaçõesRESUMO
The modulation of the immune response has been used as therapy for clinical disorders associated with human T-lymphotropic virus type 1 (HTLV-1) infection. In this study, the cytokine profile was evaluated in 26 asymptomatic HTLV-1 blood donors. Additionally, both the cell responsible for producing interferon-gamma (IFN-gamma) and the role of exogenous interleukin (IL)-10 in downregulating IFN-gamma production were studied. Cytokine levels were determined in supernatants of unstimulated lymphocyte cultures by enzyme-linked immunosorbent assay. The levels of IFN-gamma, tumor necrosis factor-alpha, IL-5, and IL-10 were higher in supernatants of the lymphocyte cultures taken from HTLV-1-infected donors than in those taken from healthy subjects. Although depletion of CD8+ T cells and natural killer cells did not affect IFN-gamma production, depletion of CD4+ T cells significantly decreased IFN-gamma production. Furthermore, at a concentration of 2 ng/ml, IL-10 had only a minimum effect on IFN-gamma production, although at high concentrations (100 ng/ml), IL-10 decreased IFN-gamma production by 50% in HTLV-1-infected individuals. These data indicate that both T helper 1 and T helper 2 cytokines are elevated in HTLV-1 infection and that IL-10 in high concentrations modulates IFN-gamma production in these patients.