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.
abstract: 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.
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, Brazil.
authors.forename: Lúcia Cristina Jamli
authors.initials: LC
authors.lastname: Abel
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, Brazil ; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, 01246-000 São Paulo, SP, Brazil ; Institute for Investigation in Immunology (III), INCT, 05403-001 São Paulo, SP, Brazil.
authors.forename: Ludmila Rodrigues Pinto
authors.initials: LR
authors.lastname: Ferreira
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, Brazil ; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, 01246-000 São Paulo, SP, Brazil ; Institute for Investigation in Immunology (III), INCT, 05403-001 São Paulo, SP, Brazil.
authors.forename: Isabela
authors.initials: I
authors.lastname: Cunha Navarro
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, Brazil ; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, 01246-000 São Paulo, SP, Brazil ; Institute for Investigation in Immunology (III), INCT, 05403-001 São Paulo, SP, Brazil.
authors.forename: Monique Andrade
authors.initials: MA
authors.lastname: Baron
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, Brazil ; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, 01246-000 São Paulo, SP, Brazil ; Institute for Investigation in Immunology (III), INCT, 05403-001 São Paulo, SP, Brazil.
authors.forename: Jorge
authors.initials: J
authors.lastname: Kalil
authors.affiliation: Research Center René Rachou, Oswaldo Cruz Foundation (FIOCRUZ), 30190-002 Belo Horizonte, MG, Brazil ; Laboratory of Immunopathology, Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, 31270-910 Belo Horizonte, MG, Brazil ; Division of Infectious Diseases and Immunology, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USA.
authors.forename: Ricardo Tostes
authors.initials: RT
authors.lastname: Gazzinelli
authors.affiliation: Hospital Israelita Albert Einstein, Avenida Albert Einstein 627-701, 2 Subsolo Bloco A., 05651-901 São Paulo, SP, Brazil.
authors.forename: Luiz Vicente
authors.initials: LV
authors.lastname: Rizzo
authors.affiliation: Laboratory of Immunology, Heart Institute (InCor), School of Medicine, University of São Paulo, 05403-001 São Paulo, SP, Brazil ; Division of Clinical Immunology and Allergy, School of Medicine, University of São Paulo, 01246-000 São Paulo, SP, Brazil ; Institute for Investigation in Immunology (III), INCT, 05403-001 São Paulo, SP, Brazil.
authors.forename: Edecio
authors.initials: E
authors.lastname: Cunha-Neto
mesh_terms: D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism*; D002478:Cells, Cultured; D006023:Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D017261:Glycosylphosphatidylinositols / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism*; D009000:Monocytes / Q000378:metabolism*; D009077:Mucins / Q000737:chemistry*; D011485:Protein Binding; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D019013:CD40 Antigens; D006023:Glycoproteins; D017261:Glycosylphosphatidylinositols; D009077:Mucins; D023201:CD40 Ligand; D018664:Interleukin-12; D007371:Interferon-gamma