TLR2 modulates inflammation in zymosan-induced arthritis in mice.
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.
Frasnelli
Matthias E
ME
Laboratoire de Rhumatologie, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Matthias.Frasnelli@hospvd.ch
Tarussio
David
D
Chobaz-Péclat
Veronique
V
Busso
Nathalie
N
So
Alexander
A
D000818:Animals; D001169:Arthritis, Experimental / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D003176:Complement C3 / Q000172:deficiency / Q000502:physiology; D005260:Female; D005936:Glucans; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000096:biosynthesis; D037181:Lectins, C-Type; D008213:Lymphocyte Activation; D008264:Macrophages / Q000187:drug effects / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D010587:Phagocytosis / Q000187:drug effects; D011134:Polysaccharides / Q000494:pharmacology; D011877:Radionuclide Imaging; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013997:Time Factors; D051195:Toll-Like Receptor 2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015054:Zymosan / Q000276:immunology / Q000633:toxicity*; D000099181:Dectin-1
D003176:Complement C3; D005936:Glucans; D007074:Immunoglobulin G; D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011134:Polysaccharides; D051195:Toll-Like Receptor 2; D015054:Zymosan; D000099181:Dectin-1; C493486:Tlr2 protein, mouse; C008247:laminaran
Nature. 1999 Oct 21;401(6755):811-5
10548109
Science. 1958 Apr 4;127(3301):756-7
13543326
Cytokine. 1999 Dec;11(12):1046-56
10623430
J Biol Chem. 2000 Jun 30;275(26):20157-67
10779524
Proc Natl Acad Sci U S A. 2000 Dec 5;97(25):13766-71
11095740
Nature. 2001 Sep 6;413(6851):36-7
11544516
Annu Rev Immunol. 2002;20:825-52
11861619
J Leukoc Biol. 2002 Jul;72(1):140-6
12101273
J Exp Med. 2002 Aug 5;196(3):407-12
12163569
J Immunol. 2002 Oct 1;169(7):3876-82
12244185
Am J Pathol. 2003 Apr;162(4):1221-7
12651614
J Exp Med. 2003 May 5;197(9):1119-24
12719478
J Immunol. 2003 May 15;170(10):5075-81
12734352
J Endotoxin Res. 2003;9(3):176-80
12831459
J Immunol. 2004 Jan 15;172(2):1157-62
14707091
Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):3029-34
14981245
J Leukoc Biol. 2004 Apr;75(4):649-56
14726497
Arthritis Res Ther. 2004;6(3):R256-63
15142272
Arthritis Rheum. 2004 May;50(5):1457-67
15146415
J Reticuloendothel Soc. 1970 Nov;8(5):465-73
5471976
Proc Natl Acad Sci U S A. 1977 Apr;74(4):1683-7
266208
Immunology. 1977 Jun;32(6):929-40
328387
Arthritis Rheum. 1977 Sep-Oct;20(7):1396-1401
911357
Agents Actions. 1981 Dec;11(6-7):640-2
6280467
Complement. 1987;4(2):61-74
3040332
Arthritis Rheum. 1995 Feb;38(2):164-72
7848306
Proc Natl Acad Sci U S A. 1995 Dec 5;92(25):11490-4
8524789
J Immunol. 1996 May 1;156(9):3418-25
8617968
Nature. 1997 Jul 24;388(6640):394-7
9237759
Nature. 1998 Mar 19;392(6673):245-52
9521319
J Biol Chem. 1998 Aug 21;273(34):22014-20
9705343
J Biol Chem. 1999 Jun 18;274(25):17406-9
10364168
Science. 1999 Jul 30;285(5428):736-9
10426996
Immunity. 1999 Oct;11(4):443-51
10549626