β-1,4-mannobiose stimulates innate immune responses and induces TLR4-dependent activation of mouse macrophages but reduces severity of inflammation during endotoxemia in mice.
β-1,4-Mannobiose (MNB) has been shown to exert prebiotic activity and modulate mucosal gene expression. In this study, the immune-modulating effect of MNB in healthy and endotoxemic mice and its role in Toll-like receptor (TLR) 2/4-mediated macrophage activation were investigated. Mice were supplemented daily with MNB (0, 5, 10, or 25 mg/kg) for 14 d. To examine the effect of MNB during endotoxemia, mice were supplemented with or without MNB (25 mg/kg) for 14 d, followed by challenge with intraperitoneal LPS or saline. MNB induced expression of both T helper (Th) 1- and Th2-type cytokines in the ileum (P < 0.05) and increased fecal IgA production and splenic NK cell activity (P < 0.05) in healthy mice. In endotoxemic mice, MNB reduced the expression of Tnfa, Il-6, iNos (P < 0.05), and Il-10 (P < 0.05), and reduced LPS-induced weight loss but increased Ifng, Il-12p40, Il-5, and Ifna expression (P < 0.05) and NK cell activity relative to positive control (LPS) mice. Treatment of RAW 264.7 macrophages with MNB induced TNF-α and IL-6 secretion (P < 0.05), and this effect was abrogated by inhibiting TLR4, but not TLR2, signaling. Pretreatment of RAW 264.7 cells with MNB induced tolerance to TLR2 and TLR4 agonists, reducing TNF-α production (P < 0.05) upon secondary stimulation with LPS or lipoteichoic acid. These results indicate that MNB can modulate intestinal and systemic immune responses in healthy and endotoxemic mice and prevent LPS-induced immune suppression, as well as directly stimulating innate immune mechanisms in vitro as a TLR4 agonist.
Department of Food Science, University of Guelph, Guelph, Canada.
Jennifer
J
Kovacs-Nolan
Hiroyuki
H
Kanatani
Akihiro
A
Nakamura
Masahisa
M
Ibuki
Yoshinori
Y
Mine
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D016207:Cytokines / Q000378:metabolism; D019587:Dietary Supplements; D019446:Endotoxemia / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D005243:Feces / Q000737:chemistry; D005260:Female; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007113:Immunity, Innate / Q000187:drug effects*; D007070:Immunoglobulin A / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism*; D008070:Lipopolysaccharides; D008264:Macrophages / Q000187:drug effects*; D008351:Mannans / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D056692:Prebiotics; D012720:Severity of Illness Index; D012965:Sodium Chloride; D013154:Spleen / Q000187:drug effects / Q000276:immunology; D013682:Teichoic Acids; D018417:Th1 Cells / Q000187:drug effects; D018418:Th2 Cells / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism
D000276:Adjuvants, Immunologic; D016207:Cytokines; D007070:Immunoglobulin A; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D008351:Mannans; D056692:Prebiotics; D013682:Teichoic Acids; D051197:Toll-Like Receptor 4; C014647:mannobiose; D012965:Sodium Chloride; C009900:lipoteichoic acid