title: Glycoinositolphospholipids from Trypanosoma cruzi interfere with macrophages and dendritic cell responses.
abstract: To investigate the possible effects of glycoinositolphospholipid (GIPL) from Trypanosoma cruzi on human antigen presenting cells, we tested their effects on lipopolysaccharide (LPS)-stimulated human macrophages and dendritic cells (DC). Human macrophages or DC were incubated with GIPL (50 microg/ml) and LPS (500 pg/ml) and tumor necrosis factor alpha (TNF-alpha), interleukin 8 (IL-8), IL-10, and IL-12p40 levels in supernatants were analyzed by enzyme-linked immunosorbent assay. TNF-alpha, IL-10, and IL-12 secretion were significantly decreased by GIPL both in macrophages and DC. In contrast, GIPL did not alter IL-8 production. We also analyzed the expression of CD80, CD86, HLA-DR, CD40, and CD57 on the macrophage surface after stimulation with LPS in the presence or absence of T. cruzi GIPL. GIPL led to a down-regulation in the expression of all tested molecules. We additionally examined the influence of T. cruzi GIPL on the response of human DC to LPS. LPS-induced HLA-DR, CD83, and CD86 up-regulation was significantly inhibited by GIPL. A slight down-regulation in CD80 and CD40 expression on DC surfaces in the presence of GIPL was also noticed. Similarly, GIPL led to down-modulation of CD83, CD80, CD86, and HLA-DR surface expression and TNF-alpha and IL-10 production when DC were stimulated by CD40L. The ceramide portion of GIPL was responsible for most of the activity exhibited by the whole molecule. Considering the important role of the immune response in determining the fate of the host-parasite relationship, the immunoregulatory activities of T. cruzi GIPL are potentially important for parasite evasion and then pathogenesis of infection with protozoan parasites.
authors.affiliation: Centro de Pesquisa Gonçalo Moniz, FIOCRUZ, Instituto de Ciências da Saúde, Universidade Federal Bahia, Salvador, Brazil.
authors.forename: Claudia
authors.initials: C
authors.lastname: Brodskyn
authors.forename: Julie
authors.initials: J
authors.lastname: Patricio
authors.forename: Rubem
authors.initials: R
authors.lastname: Oliveira
authors.forename: Lucas
authors.initials: L
authors.lastname: Lobo
authors.forename: Andrea
authors.initials: A
authors.lastname: Arnholdt
authors.forename: Lucia
authors.initials: L
authors.lastname: Mendonça-Previato
authors.forename: Aldina
authors.initials: A
authors.lastname: Barral
authors.forename: Manoel
authors.initials: M
authors.lastname: Barral-Netto
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen; D002478:Cells, Cultured; D002518:Ceramides / Q000276:immunology; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D006017:Glycolipids / Q000276:immunology* / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D018664:Interleukin-12 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010743:Phospholipids / Q000276:immunology* / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497964:CD86 protein, human; D002518:Ceramides; D006017:Glycolipids; D006684:HLA-DR Antigens; D016209:Interleukin-8; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D010743:Phospholipids; D014409:Tumor Necrosis Factor-alpha; C115336:glycoinositolphospholipid, Trypanosoma; D018799:Intercellular Adhesion Molecule-1; D016753:Interleukin-10; D018664:Interleukin-12