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 (99)Tc 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; (99)Tc 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.