Helminth parasites are known to alter host immune responses and the responsible molecules are a potential source of biological immunoadjuvants. Previously, we have reported strong Th-2 type immunomodulatory properties of Taenia crassiceps glycans. In this study, we report interferon-gamma (IFN-gamma) stimulatory activity of fractionated Taenia glycans and Lewis sugars with comparable glycan composition. Our data show that Taenia glycans and Lewis X pentasaccharide are potent stimulators of the Th-1 type cytokine IFN-gamma. We postulate that the terminal beta-(1-4)-galactose residue in Lewis X is associated with IFN-gamma stimulation from naive BALB/c mouse spleen and peritoneal exudate cells. Antibodies to toll-like receptors (TLRs) inhibited the Lewis X-induced IFN-gamma secretion. Lewis X up-regulated the expression of NF-kappaB p65 from naive spleen cells and IFN-gamma transcription in peritoneal exudate cells. These data demonstrate the ability of Lewis type helminth glycans to modulate host responses in a Th-1 direction via NF-kappaB p65, IFN-gamma and macrophage TLRs.