Induction of experimental allergic arthritis with outer surface proteins of borrelia burgdorferi

Abstract

Objective. The arthritogenic potential of the cationic outer surface proteins (Osp) from Borrelia burgdorferi was tested in rats.Methods. Water-soluble Osps were prepared by butanol extraction and were administered by intraarticular injection. Tissue injury was assessed by scintigraphy and histology.Results. A mild arthritis was seen in naive rats. Preimmunized animals had more severe, longer lasting bouts of inflammation.Conclusion. The Osps of Borreliu burgdorfen are potent arthritogens in rats. These immunodominant antigens may play a role in the development of Lyme arthritis in humans.Arthritis is a frequent complication of Borreliu burgdorferi infection. Up to 60% of patients with untreated erythema chronicum migrans develop Lyme arthritis. About half of these patients experience intermittent attacks of inflammation and 10% develop chronic arthritis (1). In one study, bacteria were demonstrated in discrete foci within the structures of arthritic joints (2), and successful cultivation of Borreliu from synovial fluid has also been reported in a limited number of cases (3-5). Nevertheless, whether the induction and maintainance of Lyme arthritis requires the presence of bacteria or their products within the affected joints remains an unanswered question. There are approaches for establishing animal models of Lyme arthritis using live organisms. In rats and mice, the severity of arthritis following infection was found to be age dependent; young animals developed more severe inflammation (6,7). Arthritis has also been induced by injecting B burgdorferi into the joints of irradiated hamsters (8). In immunodeficient SCID mice, Borreliu infection leads to persistent spirochetemia, accompanied by multiple organ manifestations, including chronic joint inflammation (9). These models have increased our understanding of the biology of Lyme disease. It appears that arthritis develops best when the host animal's immune system is either immature or blatantly compromised. The underlying immunopathogenic mechanisms leading to Lyme arthritis in the presence of an intact immune system have not yet been clarified.Previous studies of rodents have shown that cationic antigens, including bacterial products, can be potent inducers of allergic arthritis (10-13); anionic antigens are not effective in this experimental setting (for review, see ref. 13). Postulating that the inflammatory process characteristic of Lyme arthritis may be an antigen-driven event, we sought putative cationic arthritogens from B burgdorferi. The most abundant cationic molecules possessed by B burgdorferi are the outer surface proteins (Osps) (14,15), which are also the immunodominant antigens in chronic borrelial infection (15,16). We were able to show that the Osps, in complexed form, are capable of inducing severe joint disease in healthy adult rats. MATERIALS AND METHODSAntigens. The Osp complex was prepared from B burgdorferi in aqueous form, as described previously (17). Briefly, late log cultures of B burgdorferi strains GeHo (a Freiburg area skin isol...

Outer surface lipoproteins ofBorrelia burgdorferivary in their ability to induce experimental joint injury

“…Local inflammation initiated by OSPs, particularly OspA, is a potential major mechanism in the acute phase of Lyme arthritis. In addition to the experimental evidence presented here and previously (13), development of arthritis in humans during B burgdorferi infection is associated with humoral and cellular immune responses to borrelial antigens, including OspA (37)(38)(39). A temporal relationship between the appearance of antibody to OspA and the onset of joint inflammation was previously reported (40).…”

“…Synthetic lipohexapeptide analogs of treponemal and borrelial lipoproteins have been shown to cause acute skin lesions in mice (12). We previously demonstrated that a model of chronic arthritis could be induced in rats with a butanol-extracted, water-soluble OSP complex from B burgdorferi (13). That observation prompted the current set of experiments, which represent the first study in which the pathogenicity of individual recombinant versions of OSPs was directly studied in vivo.…”

“…First, synthetic lipopeptide analogs of treponemal and borrelial lipoproteins caused acute dermal lesions in mice (12). Second, an OSP complex extracted from B burgdorferi induced severe, chronic arthritis in rats (13). In the current study, 3 major OSPs (OspA, OspB, and OspC) derived from B burgdorferi were studied.…”

IL-10 Deficiency Promotes Increased Borrelia burgdorferi Clearance Predominantly through Enhanced Innate Immune Responses

“…Introduction of B. burgdorferi into skin or joint tissues elicits rapid migration of inflammatory cells, primarily PMN and M into the infected areas (64,78). In infected humans and some animal species, many develop an erythema migrans skin lesion emanating from the inoculation site, that is believed to represent the tissue reaction to inflammatory mediators produced by host inflammatory cells in response to the disseminating spirochetes (2).…”

Toll-Like Receptor 2 Is Required for Innate, But Not Acquired, Host Defense to Borrelia burgdorferi

“…These lipoproteins are potent stimulants of proinflammatory products in numerous cell types, including macrophages, endothelial cells, neutrophils, and B lymphocytes (3)(4)(5)(6). Injection of lipoproteins or lipopeptides into joints or skin induces an acute inflammatory infiltrate consisting predominantly of neutrophils (7,8), suggesting that lipoproteins play a major role in inflammatory induction in vivo. The recent identification of TLR2 as the signal-transducing receptor for bacterial lipoproteins leading to nuclear translocation of the inflammatory transcription factor NF-B provides a mechanism for the initiation and modification of inflammatory events associated with Lyme disease (3, 9 -13).…”