Induction of Experimental Arthritis by Borrelial Lipoprotein and CpG Motifs: Are Toll-Like Receptors 2, 4, 9 or CD-14 Involved?



Stephen Batsford1, *, John Dunn2, Michael Mihatsch3
1 Department of Immunology, Institute of Medical Microbiology and Hygiene, Albert Ludwigs University Freiburg, D-79104 Germany
2 Brookhaven National Laboratory, Upton, New York 11973, USA
3 Institute of Pathology, Kantonspital Basel, CH-4003 Switzerland


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© Batsford et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the Department of Immunology, Institute of Medical Microbiology, Hermann-Herder-Strasse 11, University Hospital Freiburg, D-79104 Freiburg, Germany; Tel: ++ 49-761-203-6552/20; Fax: ++ 49-761-203-6577; E-mail: stephen.batsford@uniklinik-freiburg.de


Abstract

Bacterial lipoproteins and CpG-DNA are ligands for Toll-Like-Receptors (TLR) 2 and 9 respectively. Both classes of molecules were reported to induce experimental arthritis in rodents following direct intra-articular injection. Here we studied: 1) whether arthritis induction by Outer surface (Lipo)protein A (OspA) (B.burgdorferi) involved the TLR-2 as well as the TLR-4 or the CD-14 receptors in addition, and 2) re-examined the arthritogenic potential of CpG-DNA motifs in mice.

Following intra-articular injection of the test substances [20µg recombinant, lipidated OspA; 1nM(6µg) to 10nM(60µg) synthetic CpG-DNA], inflammation was monitored by 99Tc scintigraphy (ratio left/right knee joint uptake > 1.1 indicates inflammation) and by histology.

Lipoprotein OspA induced severe, acute arthritis in TLR-2+/+ w.t. but not in TLR-2-/- mice (p<0.01). There were no significant differences in the severity of arthritis induced in TLR-4+/+ w.t. and TLR-4-/- mutant mice, or between CD14+/+ w.t. and CD14-/- mice.

CpG-DNA (1or 10 nM) did not cause notable inflammation in C57BL/6 mice; 99Tc ratios were < 1.0 and histology showed only minimal changes.

Induction of arthritis by the OspA lipoprotein of B.burgdorferi involves the TLR-2 receptor, no evidence for additional participation of TLR-4 or CD14 receptors was found. Intra-articular injection of CpG-DNA did not produce manifest joint injury in mice, at variance with previous reports.

Keywords: Lipoprotein, arthritis, lipidated Osp A, CpG, CD-14, TLR-2, 4, 9..