Activation of macrophages by linear (1→3)-β-D-glucans. Implications for the recognition of fungi by innate immunity

Keiko Kataoka, Tatsushi Muta, Soh Yamazaki, Koichiro Takeshige

Research output: Contribution to journalArticlepeer-review

166 Citations (Scopus)

Abstract

Although (1→3)-β-D-glucans, which are one of major fungal cell wall components, are known to activate invertebrate innate immune systems, their activities on mammalian cells remain elusive. Here, we report their activities on mouse macrophages. Among the various (1→3)-β-D-glucans, curdlan, a linear (1→3)-β-D-glucan, although not branched β-glucans, exhibits significant activity to stimulate nuclear factor-κB in macrophages. The activity of curdlan is dramatically enhanced by pretreatment with sodium hydroxide or dimethyl sulfoxide, which disrupts multiple-stranded helices of (1→3)-β-D-glucans, and is dose-dependently inhibited by a (1→3)-β-D-glucan-binding protein and by laminarioligosaccharides with (1→3)-β-D-glucosidic linkages. Intriguingly, the activity of curdlan is also augmented by incubation with zymolyase, which releases (1→3)-β-D-glucans with a single helical structure from the glucan-networks assembled by multiple-stranded helices. The activation of macrophages culminates in the production of inducible nitric-oxide synthase, tumor necrosis factor-α, and macrophage inflammatory protein-2. Furthermore, a dominant-negative mutant of MyD88, an adaptor protein mediating signaling through the Toll-like receptor/inerleukin-1 receptor-like (TIR) domain, inhibits the activation of macrophages by curdlan. These results strongly suggest that macrophages respond to linear (1→3)-β-D-glucans, possibly released from fungal cell walls, via a receptor(s) harboring the TIR domain, such as a Toll-like receptor, to induce inflammatory reactions.

Original languageEnglish
Pages (from-to)36825-36831
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number39
DOIs
Publication statusPublished - 2002 Sep 27

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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