Immunoregulatory mechanisms in Chagas disease: modulation of apoptosis in T-cell mediated immune responses

Submitted by Nuzia Santos ([email protected]) on 2017-07-17T17:53:45Z No. of bitstreams: 1 Chaves_AnaThereza_Immunoregulatory mechanisms_IRR_2016.pdf: 12736177 bytes, checksum: 7182dae7e3675c77254aa3dd4157a0a9 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2017-07-17T18:03:09Z (GMT) No. of bitstreams: 1 Chaves_AnaThereza_Immunoregulatory mechanisms_IRR_2016.pdf: 12736177 bytes, checksum: 7182dae7e3675c77254aa3dd4157a0a9 (MD5)Made available in DSpace on 2017-07-17T18:03:09Z (GMT). No. of bitstreams: 1 Chaves_AnaThereza_Immunoregulatory mechanisms_IRR_2016.pdf: 12736177 bytes, checksum: 7182dae7e3675c77254aa3dd4157a0a9 (MD5) Previous issue date: 2016Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Laboratório de Biologia das Interações Celulares. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Faculdade de Medicina Programa de Pós graduação em Medicina Tropical e Infectologia. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilFundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Biomarcadores de Diagnóstico e Monitoração. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Morfologia. Laboratório de Biologia das Interações Celulares. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Imunologia e Genômica de Parasitos. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Fisiologia e Biofísica. Belo Horizonte, MG, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas René Rachou. Laboratório de Imunologia Celular e Molecular. Belo Horizonte, MG, BrazilUniversidade Federal de Minas Gerais. Instituto de Ciências Biológicas. Departamento de Parasitologia. Laboratório de Imunologia e Genômica de Parasitos. Belo Horizonte, MG, Brazil.Universidade Federal de Minas Gerais. Faculdade de Medicina Programa de Pós graduação em Medicina Tropical e Infectologia. Belo Horizonte, MG, Brazil.Laboratório de Imunologia Celular e Molecular, Centro de Pesquisas René Rachou, Fiocruz, Belo Horizonte, Brazil/Instituto Nacional de Ciência e Tecnologia em Doenças Tropicais. Belo Horizonte, MG, Brazil/Universidade Federal de Ouro Preto. Ouro Preto, MG, Brazil.BACKGROUND: Chronic Chagas disease presents different clinical manifestations ranging from asymptomatic (namely indeterminate) to severe cardiac and/or digestive. Previous results have shown that the immune response plays an important role, although no all mechanisms are understood. Immunoregulatory mechanisms such as apoptosis are important for the control of Chagas disease, possibly affecting the morbidity in chronic clinical forms. Apoptosis has been suggested to be an important mechanism of cellular response during T. cruzi infection. We aimed to further understand the putative role of apoptosis in Chagas disease and its relation to the clinical forms of the disease. METHODS: Apoptosis of lymphocytes, under antigenic stimuli (soluble T. cruzi antigens - TcAg) where compared to that of non-stimulated cells. Apoptosis was evaluated using the expression of annexin and caspase 3(+) by T cells and the percentage of cells positive evaluated by flow cytometry. In addition activation and T cell markers were used for the identification of TCD4(+) and TCD8(+) subpopulations. The presence of intracellular and plasma cytokines were also evaluated. Analysis of the activation status of the peripheral blood cells showed that patients with Chagas disease presented higher levels of activation determined by the expression of activation markers, after TcAg stimulation. PCR array were used to evaluate the contribution of this mechanism in specific cell populations from patients with different clinical forms of human Chagas disease. RESULTS: Our results showed a reduced proliferative response associated a high expression of T CD4(+)CD62L(-) cells in CARD patients when compared with IND group and NI individuals. We also observed that both groups of patients presented a significant increase of CD4(+) and CD8(+) T cell subsets in undergoing apoptosis after in vitro stimulation with T. cruzi antigens. In CARD patients, both CD4(+) and CD8(+) T cells expressing TNF-α were highly susceptible to undergo apoptosis after in vitro stimulation. Interestingly, the in vitro TcAg stimulation increased considerably the expression of cell death TNF/TNFR superfamily and Caspase family receptors genes in CARD patients. CONCLUSIONS: Taken together, our results suggest that apoptosis may be an important mechanism for the control of morbidity in T. cruzi infection by modulating the expression of apoptosis genes, the cytokine environment and/or killing of effector cells

Immune Modulation in Primary Vaccinia virus Zoonotic Human Infections

In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, including Monkeypox, Cowpox, and Vaccinia virus (VACV). Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4+ cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans

CXCL-16, IL-17, and bone morphogenetic protein 2 (BMP-2) are associated with overweight and obesity conditions in middle-aged and elderly women.

The current concept of overweight/obesity is most likely related to a combination of increased caloric intake and decreased energy expenditure. Widespread inflammation, associated with both conditions, appears to contribute to the development of some obesity-related comorbidities. Interventions that directly or indirectly target individuals at high risk of developing obesity have been largely proposed because of the increasing number of overweight/obese cases worldwide. The aim of the present study was to assess CXCL16, IL-17, and BMP-2 plasma factors in middle-aged and elderly women and relate them to an overweight or obese status. In total, 117 women were selected and grouped as eutrophic, overweight, and obese, according to anthropometric parameters. Analyses of anthropometric and circulating biochemical parameters were followed by plasma immunoassays for CXCL-16, IL- 17, and BMP-2

Impacts of Agricultural Toxicity on Non-Target Organisms in Aquatic Ecosystem

The present review addresses the impacts of pesticides used in crops on non-target organisms in aquatic ecosystems. In recent decades, these ecosystems have received large amounts of these compounds, which are released by urban communities, rural and industrial properties. Pesticides reach the aquatic environment through different routes (leaching, irrigation, drainage, and surface runoff) and can easily reach non-target organisms, such as fish, mollusks, as well as other benthic organisms. Usually, these animals tend to undergo bioaccumulation. Exposure to these pesticides can cause numerous physiological changes by direct influence on certain cellular structures, such as on the lysosomal membrane, which can be degraded. Also, they can even react with nucleic acids resulting in several genetic injuries, thus causing adverse reactions to the body. There is a need for more incentives for the adoption of sustainable agroecological practices, as well as a ban on active ingredients harmful to the environment, in addition to strict inspection by competent environmental agencies

Clinical Study Immune Modulation in Primary Vaccinia virus Zoonotic Human Infections

In 2010, the WHO celebrated the 30th anniversary of the smallpox eradication. Ironically, infections caused by viruses related to smallpox are being increasingly reported worldwide, including Monkeypox, Cowpox, and Vaccinia virus (VACV). Little is known about the human immunological responses elicited during acute infections caused by orthopoxviruses. We have followed VACV zoonotic outbreaks taking place in Brazil and analyzed cellular immune responses in patients acutely infected by VACV. Results indicated that these patients show a biased immune modulation when compared to noninfected controls. Amounts of B cells are low and less activated in infected patients. Although present, T CD4 + cells are also less activated when compared to noninfected individuals, and so are monocytes/macrophages. Similar results were obtained when Balb/C mice were experimentally infected with a VACV sample isolated during the zoonotic outbreaks. Taking together, the data suggest that zoonotic VACVs modulate specific immune cell compartments during an acute infection in humans

Growth differentiation factor 11 delivered by dairy Lactococcus lactis strains modulates inflammation and prevents mucosal damage in a mice model of intestinal mucositis

Mucositis is an inflammation of the gastrointestinal mucosa that debilitate the quality of life of patients undergoing chemotherapy treatments. In this context, antineoplastic drugs, such as 5-fluorouracil, provokes ulcerations in the intestinal mucosa that lead to the secretion of pro-inflammatory cytokines by activating the NF-κB pathway. Alternative approaches to treat the disease using probiotic strains show promising results, and thereafter, treatments that target the site of inflammation could be further explored. Recently, studies reported that the protein GDF11 has an anti-inflammatory role in several diseases, including in vitro and in vivo results in different experimental models. Hence, this study evaluated the anti-inflammatory effect of GDF11 delivered by Lactococcus lactis strains NCDO2118 and MG1363 in a murine model of intestinal mucositis induced by 5-FU. Our results showed that mice treated with the recombinant lactococci strains presented improved histopathological scores of intestinal damage and a reduction of goblet cell degeneration in the mucosa. It was also observed a significant reduction of neutrophil infiltration in the tissue in comparison to positive control group. Moreover, we observed immunomodulation of inflammatory markers Nfkb1, Nlrp3, Tnf, and upregulation of Il10 in mRNA expression levels in groups treated with recombinant strains that help to partially explain the ameliorative effect in the mucosa. Therefore, the results found in this study suggest that the use of recombinant L. lactis (pExu:gdf11) could offer a potential gene therapy for intestinal mucositis induced by 5-FU