Taenia crassiceps carbohydrates stimulate IL-6 expression in naive 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 naive 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 WHO 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. (C) 2004 Elsevier Ltd. All rights reserved.