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

Chagas 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 immun...

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Main Authors: Lúcia Cristina Jamli Abel, Ludmila Rodrigues Pinto Ferreira, Isabela Cunha Navarro, Monique Andrade Baron, Jorge Kalil, Ricardo Tostes Gazzinelli, Luiz Vicente Rizzo, Edecio Cunha-Neto
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2014/345659
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author Lúcia Cristina Jamli Abel
Ludmila Rodrigues Pinto Ferreira
Isabela Cunha Navarro
Monique Andrade Baron
Jorge Kalil
Ricardo Tostes Gazzinelli
Luiz Vicente Rizzo
Edecio Cunha-Neto
author_facet Lúcia Cristina Jamli Abel
Ludmila Rodrigues Pinto Ferreira
Isabela Cunha Navarro
Monique Andrade Baron
Jorge Kalil
Ricardo Tostes Gazzinelli
Luiz Vicente Rizzo
Edecio Cunha-Neto
author_sort Lúcia Cristina Jamli Abel
collection DOAJ
description Chagas 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.
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spelling doaj-art-08f3f188044c412db0f1d5ae3717a1d72025-02-03T07:25:20ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/345659345659Induction of IL-12 Production in Human Peripheral Monocytes by Trypanosoma cruzi Is Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN-γ and CD40-CD40L InteractionsLúcia Cristina Jamli Abel0Ludmila Rodrigues Pinto Ferreira1Isabela Cunha Navarro2Monique Andrade Baron3Jorge Kalil4Ricardo Tostes Gazzinelli5Luiz Vicente Rizzo6Edecio Cunha-Neto7Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, BrazilLaboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, BrazilLaboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, BrazilLaboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, BrazilLaboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, BrazilResearch Center René Rachou, Oswaldo Cruz Foundation (FIOCRUZ), 30190-002 Belo Horizonte, MG, BrazilHospital Israelita Albert Einstein, Avenida Albert Einstein 627-701, 2 Subsolo Bloco A., 05651-901 São Paulo, SP, BrazilLaboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São 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.http://dx.doi.org/10.1155/2014/345659
spellingShingle Lúcia Cristina Jamli Abel
Ludmila Rodrigues Pinto Ferreira
Isabela Cunha Navarro
Monique Andrade Baron
Jorge Kalil
Ricardo Tostes Gazzinelli
Luiz Vicente Rizzo
Edecio Cunha-Neto
Induction of IL-12 Production in Human Peripheral Monocytes by Trypanosoma cruzi Is Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN-γ and CD40-CD40L Interactions
Mediators of Inflammation
title Induction of IL-12 Production in Human Peripheral Monocytes by Trypanosoma cruzi Is Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN-γ and CD40-CD40L Interactions
title_full Induction of IL-12 Production in Human Peripheral Monocytes by Trypanosoma cruzi Is Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN-γ and CD40-CD40L Interactions
title_fullStr Induction of IL-12 Production in Human Peripheral Monocytes by Trypanosoma cruzi Is Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN-γ and CD40-CD40L Interactions
title_full_unstemmed Induction of IL-12 Production in Human Peripheral Monocytes by Trypanosoma cruzi Is Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN-γ and CD40-CD40L Interactions
title_short Induction of IL-12 Production in Human Peripheral Monocytes by Trypanosoma cruzi Is Mediated by Glycosylphosphatidylinositol-Anchored Mucin-Like Glycoproteins and Potentiated by IFN-γ and CD40-CD40L Interactions
title_sort induction of il 12 production in human peripheral monocytes by trypanosoma cruzi is mediated by glycosylphosphatidylinositol anchored mucin like glycoproteins and potentiated by ifn γ and cd40 cd40l interactions
url http://dx.doi.org/10.1155/2014/345659
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