Dendritic cell are able to differentially recognize Sporothrix schenckii antigens and promote Th1/Th17 response in vitro

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Influence of Th1/Th2 cytokines and nitric oxide in murine systemic infection induced by Sporothrix schenckii

In an attempt to elucidate the effects of Sporothrix schenckii infection on the immune response, our laboratory has developed a murine model of disseminated sporotrichosis. Helper T cells can be further subdivided into Th1 and Th2 phenotypes. The differentiation of two subsets of T lymphocytes is driven by IL-12 and IL-4 cytokines, respectively. Th1 cells produce IFN-gamma that activate macrophages and promote cell-mediated immunity. In addition, we found low levels of iNOS and NO production in the initial (1st and 2nd weeks) and final (9th and 10th weeks) periods of the infection, in contrast with the period of week 4 to 7 of elevated values. The determination of IFN-gamma and IL-12 are in agreement with NO/iNOS detection, showing the presence of cellular immune response throughout the infectious process. However, the production of IL-4 shows an increase in levels after the 5th and 6th weeks suggesting a participation of Th2 response in this period as well. Regarding these results, the study demonstrated that in experimental sporotrichosis infection the cellular immune response participated throughout the period analyzed as a nitric oxide dependent mechanism. In contrast, the presence of Th2 response began in the 5th week, suggesting the participation of humoral immune response in advanced stages of sporotrichosis.

Th1 polarized response induced by intramuscular DNA-HSP65 immunization is preserved in experimental atherosclerosis

We previously reported that a DNA vaccine constructed with the heat shock protein (HSP65) gene from Mycobacterium leprae (DNA-HSP65) was protective and also therapeutic in experimental tuberculosis. By the intramuscular route, this vaccine elicited a predominant Th1 response that was consistent with its protective efficacy against tuberculosis. It has been suggested that the immune response to Hsp60/65 may be the link between exposure to microorganisms and increased cardiovascular risk. Additionally, the high cholesterol levels found in atherosclerosis could modulate host immunity. In this context, we evaluated if an atherogenic diet could modulate the immune response induced by the DNA-HSP65 vaccine. C57BL/6 mice (4-6 animals per group) were initially submitted to a protocol of atherosclerosis induction and then immunized by the intramuscular or intradermal route with 4 doses of 100 µg DNA-HSP65. on day 150 (15 days after the last immunization), the animals were sacrificed and antibodies and cytokines were determined. Vaccination by the intramuscular route induced high levels of anti-Hsp65 IgG2a antibodies, but not anti-Hsp65 IgG1 antibodies and a significant production of IL-6, IFN-g and IL-10, but not IL-5, indicating a Th1 profile. Immunization by the intradermal route triggered a mixed pattern (Th1/Th2) characterized by synthesis of anti-Hsp65 IgG2a and IgG1 antibodies and production of high levels of IL-5, IL-6, IL-10, and IFN-g. These results indicate that experimentally induced atherosclerosis did not affect the ability of DNA-HSP65 to induce a predominant Th1 response that is potentially protective against tuberculosis.

Th1/Th2 cytokines' expression and production by propolis-treated mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Propolis effect on Th1/Th2 cytokines production by acutely stressed mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Th1/Th2 cytokine production by clove-treated mice

Although clove possesses several biological and therapeutic properties, its immunomodulatory action has not been fully investigated. The goal of this work was to investigate the effect of administration of the water extract of clove over a short-term to BALB/c mice on Th1 (IFN-gamma and IL-2) and Th2 (IL-4 and IL-10) cytokine production. After treatment, spleen cells were aseptically removed and cells were stimulated with concanavalin A. Supernatants of cell cultures were used for cytokine determination by ELISA. The chemical composition of the extract was also carried out, revealing that eugenol(4-allyl-2-methoxyphenol) was the major component in our sample. Although the anti-inflammatory action of clove has been mentioned, our data showed that clove administration to mice did not influence the Th1/Th2 cytokine balance. Further studies dealing with cytokine expression and production will provide a better understanding of clove's immunomodulatory and anti-inflammatory actions, using different extract concentrations and different intake periods.

The Effect of Propolis on Th1/Th2 Cytokine Expression and Production by Melanoma-bearing Mice Submitted to Stress

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Proteins of Leishmania (Viannia) shawi confer protection associated with Th1 immune response and memory generation

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Produção deficiente de citocinas Th1 em camundongos BALB/c jovens

O objetivo do presente estudo foi comparar a produção de IFN-γ, IL-12 e IL-4 entre camundongos jovens (5, 12 e 19 dias de idade) e adultos (30 dias de idade). As avaliações foram feitas por estimulação, in vitro, de células esplênicas com Concanavalina A (ConA) , Staphylococcus aureus (S. aureus) e lipopolissacarídeo (LPS). Diferentes concentrações de cada estímulo foram testadas e os sobrenadantes das culturas foram coletados após 48 horas de incubação e as concentrações de IFN-γ, IL-12 e IL-4 determinadas por ELISA. Células de camundongos jovens e adultos produziram níveis igualmente elevados de IFN-γ após estímulo com ConA. Somente animais adultos produziram IFN-γ em resposta ao estímulo com S. aureus. Em culturas estimuladas com LPS, a produção desta citocina foi baixa e similar nos animais jovens e significativamente elevada nos animais adultos. Somente células de animais adultos estimuladas com S. aureus foram capazes de produzir IL-12. O único estímulo capaz de induzir níveis detectáveis de IL-4 foi ConA, sendo que estes níveis foram mais elevados nos animais com 12 e 19 dias de idade em comparação com animais neonatos e adultos. A diminuição das doses ótimas dos estímulos não mudou o perfil de produção de cada citocina nos animais jovens. Estes resultados permitem concluir que a idade afeta a produção de citocinas: ocorre maior produção de IL-4 em camundongos jovens e maior produção de IL-12 e IFN-γ em animais adultos. Estas informações são importantes devido ao papel destas citocinas na polarização das respostas imunes nos sentidos Th1 e Th2. Palavras-chave: camundongo; citocina; interferon-gama; interleucina-4; interleucina-12.

Influência das células dendríticas das placas de peyer na modulação das repostas Th1/Th2 em camundongos infectados com Yersinia pseudotuberculosis

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Dicotomia Th1/Th2: papel do óxido nítrico e citocinas na esporotricose

Pós-graduação em Biociências e Biotecnologia Aplicadas à Farmácia - FCFAR

Papel de neutrófilos humanos no direcionamento da resposta imune adaptativa do tipo Th1 contra o Paracoccidioides brasiliensis

Pós-graduação em Doenças Tropicais - FMB

Carbohydrate and glutamine supplementation modulates the Th1/Th2 balance after exercise performed at a simulated altitude of 4500 m

Objective: The aim of this study was to evaluate the effect of carbohydrate or glutamine supplementation, or a combination of the two, on the immune system and inflammatory parameters after exercise in simulated hypoxic conditions at 4500 m.Methods: Nine men underwent three sessions of exercise at 70% VO2(peak) until exhaustion as follows: 1) hypoxia with a placebo; 2) hypoxia with 8% maltodextrin (200 mL/20 min) during exercise and for 2 h after; and 3) hypoxia after 6 d of glutamine supplementation (20 g/d) and supplementation with 8% maltodextrin (200 mL/20 min) during exercise and for 2 h after. All procedures were randomized and double blind. Blood was collected at rest, immediately before exercise, after the completion of exercise, and 2 h after recovery. Glutamine, cortisol, cytokines, glucose, heat shock protein-70, and erythropoietin were measured in serum, and the cytokine production from lymphocytes was measured.Results: Erythropoietin and interleukin (IL)-6 increased after exercise in the hypoxia group compared with baseline. IL-6 was higher in the hypoxia group than pre-exercise after exercise and after 2 h recovery. Cortisol did not change, whereas glucose was elevated post-exercise in the three groups compared with baseline and pre-exercise. Glutamine increased in the hypoxia + carbohydrate + glutamine group after exercise compared with baseline. Heat shock protein-70 increased post-exercise compared with baseline and pre-exercise and after recovery compared with pre-exercise, in the hypoxia carbohydrate group. No difference was observed in IL-2 and IL-6 production from lymphocytes. IL-4 was reduced in the supplemented groups.Conclusion: Carbohydrate or glutamine supplementation shifts the T helper (Th)1/Th2 balance toward Th1 responses after exercise at a simulated altitude of 4500 m. The nutritional strategies increased in IL-6, suggesting an important anti-inflammatory effect. (C) 2014 Elsevier Inc. All rights reserved.