TLR2 modulates inflammation in zymosan-induced arthritis in mice

Arthritis Res Ther. 2005;7(2):R370-9. doi: 10.1186/ar1494. Epub 2005 Jan 21.


The interplay between the innate and acquired immune systems in chronic inflammation is not well documented. We have investigated the mechanisms of inflammation in murine zymosan-induced arthritis (ZIA) in the light of recent data on the roles of Toll-like receptor 2 (TLR2) and Dectin-1 in the activation of monocyte/macrophages by zymosan. The severity of inflammation, joint histology, lymphocyte proliferation and antibody production in response to zymosan were analyzed in mice deficient in TLR2 and complement C3, and the effects of Dectin-1 inhibition by laminarin were studied. In comparison with wild-type animals, TLR2-deficient mice showed a significant decrease in the early (day 1) and late phases (day 24) of joint inflammation. C3-deficient mice showed no differences in technetium uptake or histological scoring. TLR2-deficient mice also showed a significant decrease in lymph node cell proliferation in response to zymosan and a lower IgG antibody response to zymosan at day 25 in comparison with wild-type controls, indicating that TLR2 signalling has a role in the development of acquired immune responses to zymosan. Although laminarin, a soluble beta-glucan, was able to significantly inhibit zymosan uptake by macrophages in vitro, it had no effect on ZIA in vivo. These results show that ZIA is more prolonged than was originally described and involves both the innate and acquired immune pathways. C3 does not seem to have a major role in this model of joint inflammation.

MeSH terms

  • Animals
  • Arthritis, Experimental / chemically induced
  • Arthritis, Experimental / diagnostic imaging
  • Arthritis, Experimental / metabolism
  • Arthritis, Experimental / pathology*
  • Cell Division
  • Cells, Cultured / drug effects
  • Cells, Cultured / physiology
  • Complement C3 / deficiency
  • Complement C3 / physiology
  • Female
  • Glucans
  • Immunity, Innate
  • Immunoglobulin G / biosynthesis
  • Lectins, C-Type
  • Lymphocyte Activation
  • Macrophages / drug effects
  • Macrophages / physiology
  • Male
  • Membrane Proteins / antagonists & inhibitors
  • Membrane Proteins / physiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / antagonists & inhibitors
  • Nerve Tissue Proteins / physiology
  • Phagocytosis / drug effects
  • Polysaccharides / pharmacology
  • Radionuclide Imaging
  • T-Lymphocyte Subsets / immunology*
  • Time Factors
  • Toll-Like Receptor 2 / deficiency
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / physiology*
  • Zymosan / immunology
  • Zymosan / toxicity*


  • Complement C3
  • Glucans
  • Immunoglobulin G
  • Lectins, C-Type
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Polysaccharides
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • dectin 1
  • laminaran
  • Zymosan