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Mol Immunol ; 41(4): 391-8, 2004 Jun.
Article in English | MEDLINE | ID: mdl-15163536

ABSTRACT

In murine infections of Schistosoma mansoni and Taenia crassiceps, a characteristic polarization of the immune response from a Th-1 type to a Th-2 type occurs with progression of infection. In S. mansoni, egg glycoprotein carbohydrates are said to be responsible for this immunomodulatory activity. We have previously shown that in vitro systems, T. crassiceps carbohydrates (TCHO) up-regulate the expression of interleukin 6 (IL-6) in naïve spleen cells, while conventional Th-2 cytokines were not detected. In this report, we show that peritoneal macrophages are the source of this early IL-6 and that these cells recognize T. crassiceps carbohydrates via Toll-like receptors (TLRs). Co-stimulation experiments with synthetic sugars showed that the most likely active moieties in TCHO are Lewis X analogues. To our knowledge, this is the first report on native carbohydrates of a helminth parasite stimulating mammalian innate immune cells to produce a Th-2 polarizing cytokine (IL-6) via a Toll-like receptor. It is hypothesized this is a general mechanism of Th-2 immunodominance in helminth infections in mammalian hosts.


Subject(s)
Antigens, Helminth/immunology , Carbohydrates/immunology , Gene Expression Regulation/immunology , Interleukin-6/biosynthesis , Macrophages, Peritoneal/immunology , Membrane Glycoproteins/physiology , Receptors, Cell Surface/physiology , Taenia/immunology , Th2 Cells/drug effects , Animals , Cells, Cultured/immunology , Cells, Cultured/metabolism , Egg Proteins/immunology , Immunity, Innate , Immunodominant Epitopes/immunology , Interleukin-6/genetics , Interleukin-6/metabolism , Lewis X Antigen/immunology , Macrophages, Peritoneal/metabolism , Mice , Mice, Inbred BALB C , Molecular Weight , Oligosaccharides/chemical synthesis , Oligosaccharides/immunology , Schistosoma mansoni/immunology , Spleen/cytology , Th2 Cells/immunology , Th2 Cells/metabolism , Toll-Like Receptors
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