Taenia crassiceps carbohydrates stimulate IL-6 expression in naïve murine macrophages via Toll-like receptors (TLRs).
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.
Dissanayake
Senarath
S
Department of Medical Microbiology, Faculty of Medicine, UAE University, P.O. Box 17666, Al Ain, United Arab Emirates. sendiss@uaeu.ac.ae
Amith
Ray S
RS
Shahin
Allen
A
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D002241:Carbohydrates / Q000276:immunology*; D002478:Cells, Cultured / Q000276:immunology / Q000378:metabolism; D004527:Egg Proteins / Q000276:immunology; D005786:Gene Expression Regulation / Q000276:immunology*; D007113:Immunity, Innate; D016056:Immunodominant Epitopes / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D016256:Lewis X Antigen / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008970:Molecular Weight; D009844:Oligosaccharides / Q000138:chemical synthesis / Q000276:immunology; D011956:Receptors, Cell Surface / Q000502:physiology*; D012550:Schistosoma mansoni / Q000276:immunology; D013154:Spleen / Q000166:cytology; D013621:Taenia / Q000276:immunology*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051193:Toll-Like Receptors
D000947:Antigens, Helminth; D002241:Carbohydrates; D004527:Egg Proteins; D016056:Immunodominant Epitopes; D015850:Interleukin-6; D016256:Lewis X Antigen; D008562:Membrane Glycoproteins; D009844:Oligosaccharides; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors