RESUMO
BACKGROUND: Regulatory T-cells (Tregs) are increased in patients with HTLV-1/Strongyloides stercoralis co-infection, and they may modify otherwise protective antigen-specific cytokine production. We hypothesized that effective anti-helminthic treatment would decrease Tregs and restore antigen-specific cytokine responses. METHODS/RESULTS: We enrolled 19 patients with Strongyloides larvae in their stool by Baerman's test. Six were positive and 13 negative for antibody to HTLV-1 by ELISA, with positive tests confirmed by immunoblot. Before treatment, co-infected subjects had higher Tregs percentages and lower antigen-stimulated IL-5 levels compared to subjects with Strongyloides without HTLV-1. All patients were treated with ivermectin. After effective treatment, Tregs percentages decreased in patients with HTLV-1; however, antigen-specific IL-5 production remained blunted in co-infected subjects. CONCLUSION: These results suggest that treating strongyloidiasis infection decreases circulating Tregs, but antigen-specific cytokine remains altered. This may reflect blunting of sensitization by Tregs.
Assuntos
Infecções por HTLV-I/virologia , Strongyloides stercoralis/efeitos dos fármacos , Estrongiloidíase/tratamento farmacológico , Linfócitos T Reguladores/efeitos dos fármacos , Adulto , Animais , Coinfecção/parasitologia , Coinfecção/virologia , Citocinas/efeitos dos fármacos , Citocinas/fisiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estrongiloidíase/fisiopatologia , Linfócitos T Reguladores/fisiologia , Resultado do TratamentoRESUMO
To evaluate the dynamics of regulatory T cells (Tregs) during tegumentary leishmaniasis, we assessed peripheral blood and biopsies from 54 patients. Patients with cutaneous leishmaniasis (CL) had a decreased proportion of Tregs in the peripheral blood, but the proportion was higher in the biopsies of lesions. During treatment of CL, circulating Tregs increased reaching normal proportions, whereas antigen-specific interferon-γ responses diminished. By contrast, circulating Tregs from mucosal leishmaniasis patients failed to normalize during treatment. C-C chemokine receptor type 5 was expressed on a large proportion of Tregs at the site of infection. These results demonstrate increased Tregs at the site of infection, possibly homing from the peripheral circulation.
Assuntos
Leishmania braziliensis , Leishmaniose Cutânea/imunologia , Leishmaniose Mucocutânea/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Idoso , Feminino , Humanos , Interferon gama/biossíntese , Leishmaniose Cutânea/tratamento farmacológico , Leishmaniose Mucocutânea/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Receptores CCR5/análiseRESUMO
Strongyloides stercoralis is a nematode endemic in humid tropical regions. The life cycle of this parasite is complex and unique due to its capacity to cause autoinfection, resulting in chronic infections. Innate and adaptive immune responses are responsible for clearing the parasite. Many risk factors have been described, but the most important is living in or having visited an endemic area. The clinical presentation of strongyloidiasis is varied and ranges from asymptomatic chronic infection to hyperinfection syndrome. Hyperinfection syndrome is more common in patients with immunosuppresion due to therapy with corticosteroids, coinfection with human T-lymphotropic virus type I (HTLV-1), transplant patients, or patients receiving chemotherapy. Multiplication and migration of large parasite numbers cause worsening of the initial symptoms and leads to a high mortality rate. CNS involvement in strongyloidiasis has only been seen in patients with hyperinfection syndrome. Meningitis is the most common form of CNS involvement and gram-negative bacteria are the more frequent etiology. Repeated stool samples with concentration methods have a good sensitivity and specificity. In patients that are not from endemic areas serum antibody tests may be useful in the diagnosis. Treatment with a single dose of ivermectin is recommended for most patients. In severe or hyperinfection cases repeated doses may be needed.
Assuntos
Doenças do Sistema Nervoso Central/etiologia , Doenças do Sistema Nervoso Central/parasitologia , Strongyloides stercoralis/patogenicidade , Estrongiloidíase/complicações , Animais , Doenças do Sistema Nervoso Central/diagnóstico , Doenças do Sistema Nervoso Central/terapia , Humanos , Estrongiloidíase/diagnóstico , Estrongiloidíase/imunologia , Estrongiloidíase/terapiaRESUMO
Research of human T lymphotropic virus type I (HTLV-1)-associated diseases is mostly focused on inflammatory and lymphoproliferative disorders. However, the immunosuppressive consequences of HTLV-1 infection are frequently ignored. In developing countries where exposure to parasitic and other tropical diseases is frequent, the burden of disease is significantly increased by opportunistic infections. Regulatory T cells (Tregs) are a CD4 T-cell subset capable of suppressing effector responses. During HTLV-1 infection, CD4+Foxp3+ cells are increased in HTLV-1-associated leukaemia/lymphoma (ATLL) as well as in non-leukaemic presentations. However, controversy exists regarding the actual regulatory function of these cells. In this report, we present two cases of HTLV-1 ATLL complicated by parasitic organisms and we provide a brief review of the literature regarding FoxP3+ regulatory T cells and their role as a possible mechanism for the immunosuppressive manifestations that take place during HTLV-1 infection.