A novel exopolysaccharide from the biofilm of Thermus aquaticus YT-1 induces the immune response through Toll-like receptor 2

J Biol Chem. 2011 May 20;286(20):17736-45. doi: 10.1074/jbc.M110.200113. Epub 2011 Mar 28.

Abstract

Bacterial polysaccharides are known to induce the immune response in macrophages. Here we isolated a novel extracellular polysaccharide from the biofilm of Thermus aquaticus YT-1 and evaluated its structure and immunomodulatory effects. The size of this polysaccharide, TA-1, was deduced by size-exclusion chromatography as 500 kDa. GC-MS, high performance anion-exchange chromatography with pulsed amperometric detection, electrospray ionization-MS/MS, and NMR revealed the novel structure of TA-1. The polysaccharide is composed of tetrasaccharide-repeating units of galactofuranose, galactopyranose, and N-acetylgalactosamine (1:1:2) and lacked acidic sugars. TA-1 stimulated macrophage cells to produce the cytokines TNF-α and IL-6. Screening of Toll-like receptors and antibody-blocking experiments indicated that the natural receptor of TA-1 in its immunoactivity is TLR2. Recognition of TA-1 by TLR2 was confirmed by TA-1 induction of IL-6 production in peritoneal macrophages from wild-type mice but not from TLR2(-/-) mice. TA-1, as a TLR2 agonist, could possibly be used as an adjuvant and could enhance cytokine release, which increases the immune response. Furthermore, TA-1 induced cytokine release is dependent on MyD88/TIRAP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Biofilms*
  • Carbohydrate Conformation
  • HEK293 Cells
  • Humans
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Macrophage Activation / drug effects
  • Macrophage Activation / immunology*
  • Macrophages / immunology*
  • Mice
  • Mice, Knockout
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / immunology
  • Polysaccharides, Bacterial / immunology*
  • Polysaccharides, Bacterial / pharmacology
  • Thermus / physiology*
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / immunology*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology

Substances

  • Adjuvants, Immunologic
  • IL6 protein, human
  • Interleukin-6
  • MYD88 protein, human
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Polysaccharides, Bacterial
  • TLR2 protein, human
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Tumor Necrosis Factor-alpha