Induction of IL-12 Production in Human Peripheral Monocytes by Trypanosoma cruzi Is Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN- and CD40-CD40L Interactions.

Submitted by Nuzia Santos ([email protected]) on 2015-03-02T18:01:21Z No. of bitstreams: 1 2014_132.pdf: 1484334 bytes, checksum: d096f23e5a1f9d4cd062bfcebc0ee3c2 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-03-02T18:01:57Z (GMT) No. of bitstreams: 1 2014_132.pdf: 1484334 bytes, checksum: d096f23e5a1f9d4cd062bfcebc0ee3c2 (MD5)Approved for entry into archive by Nuzia Santos ([email protected]) on 2015-03-02T18:05:44Z (GMT) No. of bitstreams: 1 2014_132.pdf: 1484334 bytes, checksum: d096f23e5a1f9d4cd062bfcebc0ee3c2 (MD5)Made available in DSpace on 2015-03-02T18:05:44Z (GMT). No. of bitstreams: 1 2014_132.pdf: 1484334 bytes, checksum: d096f23e5a1f9d4cd062bfcebc0ee3c2 (MD5) Previous issue date: 2014Universidade de São Paulo. Escola de Medicina. Instituto do Coração. Laboratory of Immunology. São Paulo, SP, BrazilUniversidade de São Paulo. Escola de Medicina. Instituto do Coração. Laboratory of Immunology. São Paulo, SP, Brazil/Universidade de São Paulo. Escola de Medicina. Clinca de Imunologia e Alergia. Sao Paulo, SP, Brazil/Institutos Nacionais de Ciência e Tecnologia. Instituto de Investigação em Imunologia. Sao Paulo, SP, BrazilUniversidade de São Paulo. Escola de Medicina. Instituto do Coração. Laboratory of Immunology. São Paulo, SP, Brazil/Universidade de São Paulo. Escola de Medicina. Clinca de Imunologia e Alergia. Sao Paulo, SP, Brazil/Institutos Nacionais de Ciência e Tecnologia. Instituto de Investigação em Imunologia. Sao Paulo, SP, BrazilUniversidade de São Paulo. Escola de Medicina. Instituto do Coração. Laboratory of Immunology. São Paulo, SP, Brazil/Universidade de São Paulo. Escola de Medicina. Clinca de Imunologia e Alergia. Sao Paulo, SP, Brazil/Institutos Nacionais de Ciência e Tecnologia. Instituto de Investigação em Imunologia. Sao Paulo, SP, BrazilUniversidade de São Paulo. Escola de Medicina. Instituto do Coração. Laboratory of Immunology. São Paulo, SP, Brazil/Universidade de São Paulo. Escola de Medicina. Clinca de Imunologia e Alergia. Sao Paulo, SP, Brazil/Institutos Nacionais de Ciência e Tecnologia. Instituto de Investigação em Imunologia. Sao Paulo, SP, BrazilFundação Oswaldo Cruz. Centro de Pesquisa Rene Rachou. Belo Horizonte, MG, Brazil/Universidade Federal de Minas Gerais. Instituto de Ciencias Biologicas.Departamento de Bioquimica e Imunologia. Laboratorio de Imunopatologia. Belo Horizonte, MG, Brazil/University of Massachusetts Medical School. Department of Medicine. Division of Infectious Diseases and Immunology. Worcester, MA, USAHospital Israelita Albert Einstein. Sao Paulo, SP, BrazilUniversidade de São Paulo. Escola de Medicina. Instituto do Coração. Laboratory of Immunology. São Paulo, SP, Brazil/Universidade de São Paulo. Escola de Medicina. Clinca de Imunologia e Alergia. Sao Paulo, SP, Brazil/Institutos Nacionais de Ciência e Tecnologia. Instituto de Investigação em Imunologia. Sao Paulo, SP, BrazilChagas disease, caused by the protozoan parasite Trypanosoma cruzi (T. cruzi), is characterized by immunopathology driven by IFN-γ secreting Th1-like T cells. T. cruzi has a thick coat of mucin-like glycoproteins covering its surface, which plays an important role in parasite invasion and host immunomodulation. It has been extensively described that T. cruzi or its products-like GPI anchors isolated from GPI-anchored mucins from the trypomastigote life cycle stage (tGPI-mucins)-are potent inducers of proinflammatory responses (i.e., cytokines and NO production) by IFN-γ primed murine macrophages. However, little is known about whether T. cruzi or GPI-mucins exert a similar action in human cells. We therefore decided to further investigate the in vitro cytokine production profile from human mononuclear cells from uninfected donors exposed to T. cruzi as well as tGPI-mucins. We observed that both living T. cruzi trypomastigotes and tGPI-mucins are potent inducers of IL-12 by human peripheral blood monocytes and this effect depends on CD40-CD40L interaction and IFN-γ. Our findings suggest that the polarized T1-type cytokine profile seen in T. cruzi infected patients might be a long-term effect of IL-12 production induced by lifelong exposure to T. cruzi tGPI-mucins

Associação de imunoestimulante com anti-helmíntico no tratamento da verminose em ovinos Association of immunostimulant with anthelmintic on the treatment of sheep verminosis

Este estudo teve como objetivo verificar a eficiência do uso de imunoestimulante associado a anti-helmíntico no tratamento das helmintoses de ovinos. Os animais do grupo I (n=29) receberam o anti-helmíntico albendazole (11mg kg-1) em administração única e o imunoestimulante composto de Propionibacterium granulosum (16ug kg-1) e lipopolissacarídeo (LPS) de Escherichia coli (1,2ug kg-1) em duas doses com intervalo de 48 horas e os animais do grupo II (n=29) receberam o anti-helmíntico albendazole (11mg kg-1). Amostras foram colhidas semanalmente durante 28 dias para a realização da contagem total e diferencial de leucócitos, hematócrito e contagem de ovos por grama de fezes (OPG). Os animais que receberam imunoestimulante associado a anti-helmíntico apresentaram aumento significativo dos valores de eosinófilos e linfócitos (P0,05). Com base nesses resultados, pode-se concluir que imunoestimulantes podem ser utilizados associados a anti-helmínticos como alternativa terapêutica no tratamento das helmintíases em ovinos, uma vez que promovem a ativação da resposta imune com participação de células e mediadores importantes para a eliminação de helmintos em ovinos.This study aimed to verify the effectiveness of the immunostimulant combined with anthelmintic on the helminthiasis treatment in sheep. The animals of group I (n=29) received the anthelmintic albendazole (11mg kg-1) in a single administration and the immunostimulant composed with Propionibacterium granulosum (16ug kg-1) and lypopolysaccharide (LPS) of Escherichia coli (1,2ug kg-1) into two doses every 48 hours and the animals from group II (n=29) received anthelmintic albendazole (11mg g-1). Samples were collected weekly during 28 days, to carry out the total and differential count of leukocytes, hematocrit and the eggs count per gram of feces (EPG). The animals that received immunostimulant combined with anthelmintic showed significantly increases of eosinophils and lymphocytes (P0.05). Based on these results it was concluded that immunostimulants can be used when combined with anthelminthic as an alternative therapy for the treatment of helminthiasis in sheep, since they promote the activation of immune response with participation of cells and mediators important for the removal of helminths in sheep