RESUMO
The Bacille Calmette-Guérin (BCG) is a potent immunomodulator. It was initially used by oral administration, but it is mostly used subcutaneously nowadays. This study shows that oral BCG vaccination modifies the immune response to a second non-related antigen (Ovalbumin) systemic immunization. Airway Ovalbumin challenge six months after the systemic intraperitoneal immunization resulted in a potent γδ+ T cell response in the lungs biased to IFN-γ and IL-17 production ex vivo and a mixed TH1, TH2, and TH17 T cells upon further stimulation with anti-CD3 mAb in vitro. Higher percentages of CD4+ T cells accompanied the augmented T cell response in oral BCG vaccinated mice. Also, the proportion of Foxp3+ Tregs was diminished compared to PBS-gavaged and OVA-immunized mice. The anti-OVA-specific antibody response was also influenced by oral exposure to BCG so that these mice produced more IgG2a and less IgE detected in the sera. These results suggest that oral BCG vaccination can modify future immune responses to vaccines and improve immunity to pathogen infections, especially in the mucosal interfaces.
Assuntos
Vacina BCG , Interleucina-17 , Animais , Vacina BCG/farmacologia , Fatores de Transcrição Forkhead , Imunidade , Imunoglobulina E , Imunoglobulina G , Interferon gama , Potenciação de Longa Duração , Camundongos , Ovalbumina , Vacinação/métodosRESUMO
Chagas disease is caused by the protozoan Trypanosoma cruzi. The parasite reaches the secondary lymphoid organs, the heart, skeletal muscles, neurons in the intestine and esophagus among other tissues. The disease is characterized by mega syndromes, which may affect the esophagus, the colon and the heart, in about 30% of infected people. The clinical manifestations associated with T. cruzi infection during the chronic phase of the disease are dependent on complex interactions between the parasite and the host tissues, particularly the lymphoid system that may either result in a balanced relationship with no disease or in an unbalanced relationship that follows an inflammatory response to parasite antigens and associated tissues in some of the host organs and/or by an autoimmune response to host antigens. This review discusses the findings that support the notion of an integrated immune response, considering the innate and adaptive arms of the immune system in the control of parasite numbers and also the mechanisms proposed to regulate the immune response in order to tolerate the remaining parasite load, during the chronic phase of infection. This knowledge is fundamental to the understanding of the disease progression and is essential for the development of novel therapies and vaccine strategies.
Assuntos
Imunidade Adaptativa , Doença de Chagas/imunologia , Doença de Chagas/patologia , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , Imunidade Inata , Trypanosoma cruzi/imunologia , Animais , Humanos , Tolerância Imunológica , Trypanosoma cruzi/patogenicidadeRESUMO
Leishmania (Leishmania) amazonensis is a protozoan that causes infections with a broad spectrum of clinical manifestations. The currently available chemotherapeutic treatments present many problems, such as several adverse side effects and the development of resistant strains. Natural compounds have been investigated as potential antileishmanial agents, and the effects of epoxy-α-lapachone on L. (L.) amazonensis were analyzed in the present study. This compound was able to cause measurable effects on promastigote and amastigote forms of the parasite, affecting plasma membrane organization and leading to death after 3 h of exposure. This compound also had an effect in experimentally infected BALB/c mice, causing reductions in paw lesions 6 weeks after treatment with 0.44 mM epoxy-α-lapachone (mean lesion area, 24.9 ± 2.0 mm(2)), compared to untreated animals (mean lesion area, 30.8 ± 2.6 mm(2)) or animals treated with Glucantime (mean lesion area, 28.3 ± 1.5 mm(2)). In addition, the effects of this compound on the serine proteinase activities of the parasite were evaluated. Serine proteinase-enriched fractions were extracted from both promastigotes and amastigotes and were shown to act on specific serine proteinase substrates and to be sensitive to classic serine proteinase inhibitors (phenylmethylsulfonyl fluoride, aprotinin, and antipain). These fractions were also affected by epoxy-α-lapachone. Furthermore, in silico simulations indicated that epoxy-α-lapachone can bind to oligopeptidase B (OPB) of L. (L.) amazonensis, a serine proteinase, in a manner similar to that of antipain, interacting with an S1 binding site. This evidence suggests that OPB may be a potential target for epoxy-α-lapachone and, as such, may be related to the compound's effects on the parasite.