Abstract
Background
Borrelia Burgdorferi has a predilection for collagenous tissue and can interact with fibronectin and cellular collagens. While the molecular mechanisms of how B. burgdorferi targets connective tissues and causes arthritis are not understood, the spirochetes can bind to a number of different cell types, including fibroblasts. A novel circulating fibroblast-like cell called the peripheral blood fibrocyte has recently been described. Fibrocytes express collagen types I and III as well as fibronectin. Besides playing a role in wound healing, fibrocytes have the potential to target to connective tissue and the functional capacity to recruit, activate, and present antigen to CD4+ T cells.
Materials and Methods
Rhesus monkey fibrocytes were isolated and characterized by flow cytometry. B. burgdorferi were incubated with human or monkey fibrocyte cultures in vitro and the cellular interactions analyzed by light and electron microscopy. The two strains of B. burgdorferi studied included JD1, which is highly pathogenic for monkeys, and M297, which lacks the cell surface OspA and OspB proteins.
Results
In this study, we demonstrate that B. burgdorferi binds to both human and monkey (rhesus) fibrocytes in vitro. This process does not require OspA or OspB. In addition, the spirochetes are not phagocytosed but are taken into deep recesses of the cell membrane, a process that may protect them from the immune system.
Conclusions
This interaction between B. burgdorferi and peripheral blood fibrocytes provides a potential explanation for the targeting of spirochetes to joint connective tissue and may contribute to the inflammatory process in Lyme arthritis.
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References
Steere AC. (1989) Lyme disease. N. Engl. J. Med. 321: 586–596.
Centers for Disease Control. (1992) Notifiable diseases report. Morbid. Mortal. Weekly Rep. 40: 898–899.
Coleman JL, Sellati TJ, Testa JE, et al. (1995) Borrelia burgdorferi binds plasminogen, resulting in enhanced penetration of endothelial monolayers. Infect. Immun. 63: 2478–2484.
Fuchs H, Wallich R, Simon MM, Kramer MD. (1994) The outer surface protein A of the spirochete Borrelia burgdorferi is a plasmin(ogen) receptor. Proc. Natl. Acad. Sci. U.S.A. 91: 12594–12598.
Hu LT, Perides G, Noring R, Klempner MS. (1995) Binding of human plasminogen to Borrelia burgdorferi. Infect. Immun. 63: 3491–3496.
Klempner MS, Noring R, Epstein MP, et al. (1994) Subversion of the host fibrinolytic pathway for invasion by the Lyme disease spirochete, Borrelia burgdorferi. In:Cevenini R, Sambri V, La Placc M (eds.) Advances in Lyme Research. Proceedings of the VI International Conference on Lyme borreliosis. pp. 997–100.
Klempner MS, Noring R, Epstein MP, et al. (1995) Binding of human plasminogen and urokinase-type plasminogen activator to the Lyme disease spirochete, Borrelia burgdorferi. J. Infect. Dis. 171: 1258–1265.
Grab DJ, Kennedy R, Philipp MT. (1996) Borrelia burgdorferi possess a collagenolytic activity. FEMS Microbiol. Lett. 144: 39–45.
Grab DJ, Didier P, Lanners HN, Adkisson HD. (1996) Proteoglycan degradation and induction of nitric oxide synthase activity of human articular cartilage by Borrelia burgdorferi. Presented at IBC 6th Annual Conference on New Therapeutic Advances in Arthritis, December 9–10, New Orleans, LA.
Williams LR, Austin FE. (1992) Hemolytic activity of Borrelia burgdorferi. Infect. Immun. 60: 3224–3230.
Georgilis K, Peacocke M, Klempner MS. (1992) Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftrixone in vitro. J. Infect. Dis. 166: 440–444.
Klempner MS, Noring R, Rogers RA. (1993) Invasion of human skin fibroblasts by the Lyme disease spirochete, Borrelia burgdorferi. J. Infect. Dis. 167: 1074–1081.
Pachner AR, Basta J, Delaney E, Hulinska D. (1995) Localization of Borrelia burgdorferi in murine Lyme borreliosis by electron microscopy. Am. J. Trop. Med. Hyg. 52: 128–123.
Coburn J, Leong JM, Erban JK. (1993) Integrin αIIbβ3 mediates binding of the Lyme disease agent Borrelia burgdorferi to human platelets. Proc. Natl. Acad. Sci. U.S.A. 90: 7059–7063.
Bucala R, Spiegel LA, Chesney J, et al. (1994) Circulating fibrocytes define a new leukocyte sub-population that mediates tissue repair. Mol. Med. 1: 71–81.
Szczepanski A, Furie MB, Benach JL, et al. (1990) Interaction between Borrelia burgdorferi and endothelium cells in vitro. J. Clin. Invest. 85: 1637–1647.
Grab DJ, Givens C, Kennedy R. (1998) Fibronectin-binding activity in Borrelia burgdorferi. Biochim. Biophys. Acta 1407: 135–145.
Barthold SW, Persing DH, Armstrong AL, et al. (1991) Kinetics of Borrelia burgdorferi dissemination and evolution of disease after intradermal inoculation of mice. Am. J. Pathol. 139: 263–273.
Häupl T, Hahn G, Rittig M, et al. (1993) Persistence of Borrelia burgdorferi in ligamentous tissue from a patient with chronic Lyme borreliosis. Arthritis Rheum. 36: 1621–1626.
Barbour AG. (1984) Isolation and cultivation of Lyme disease spirochetes. Yale J. Biol. Med. 57: 521–525.
Philipp MT, Aydintug MK, Bohm RP Jr, et al. (1993) Early and early disseminated phases of Lyme disease in the rhesus monkey: a model for infection in humans. Infect. Immun. 61: 3047–3059.
Roberts D, Bohm RP Jr, Cogswell FB, et al. (1995) Chronic Lyme disease in the rhesus monkey. Lab. Invest. 72: 146–160.
Chesney J, Bacher M, Bender A, et al. (1997) The peripheral blood fibrocyte is a potent antigen-presenting cell capable of priming naive T cells in situ. Proc. Natl. Acad. Sci. U.S.A. 94: 6307–6312.
Chesney J, Metz C, Stavitsky AB, et al. (1998) Regulated production of type I collagen and inflamatory cytokines by peripheral blood fibrocytes. J. Immunol. 160: 419–425.
Hughes CA, Engstrom SM, Coleman LA, et al. (1993) Protective immunity is induced by a Borrelia burgdorferi mutant that lacks OspA and OspB. Infect. Immun. 61: 5115–5122.
Dorward DW, Fischer ER. (1997) Lymphocyte invasion and host-cell membrane cloaking protects Borrelia burgdorferi from complement-mediated killing. In: 97th General Meeting of the American Society for Microbiology (May 4–8, Miami Beach, FL) Abstract D-133, ASM Press, Washington, D.C.
Montgomery RR, Malawista SE. (1996) Entry of Borrelia burgdorferi into macrophages is end-on and leads to degradation in lyosomes. Infect. Immun. 64: 2867–2872.
Rittig MG, Häupl T, Krause A, et al. (1994) Borrelia burgdorferi-induced ultrastructural alterations in human phagocytes: a clue to pathogenicity. J. Pathol. 173: 269–282.
Filgueira L, Nestle FO, Rittig M, Joller HI, Groscuth P. (1996) Human dendritic cells phagocytose and process Borrelia burgdorferi. J. Immunol. 7: 2998–3005.
Rittig MG, Kuhn KH, Dechant CA, et al. (1996) Phagocytes from both vertebrate and invertebrate species use “coiling” phagocytosis. Dev. Comp. Immunol. 20: 393–406.
Rittig MG, Jagoda JC, Wilske B, et al. (1998) Coiling phagocytosis discriminates between different spirochetes and is enhanced by phorbol myristate acetate and granulocyte-macrophage colony-stimulating factor. Infect. Immun. 66: 627–635.
Suhonen J, Hartiala K, Viljanen MK. (1998) Tube Phagocytosis, a novel way for neutrophils to phagocytize Borrelia burgdorferi. Infect. Immun. 66: 3433–3435.
Grab DJ, Lanners N, Didier P, Chesney J, Givens C, Kennedy R, Bucala R. (1997) Borrelia burgdorferi bind to peripheral blood fibrocytes: leukocytelike cells with potential for connective tissue targeting. FASEB J. 11: A115.
Acknowledgments
We especially acknowledge the expert technical help provided by Calvin Lancloe, Richard Kennedy, and Christina Givens (Tulane Regional Primate Research Center). We are also thankful to both Dr. Mark Wiser (Tulane University School of Public Health and Tropical Medicine) and Dr. Peter Didier (Tulane Regional Primate Research Center) for their most helpful discussions. This work was presented in part at the Experimental Biology ′97 Meetings held in New Orleans, LA, April 6–9, 1997 (33). Dennis J. Grab and H.-Norbert Lanners contributed equally to this work. Financial support for this work was provided in part by grants from the CDC (U50/CCU606604-05) and from the NCRR (P51RRAG00164-35).
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Communicated by R. Bucala
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Grab, D.J., Lanners, HN., Martin, L.N. et al. Interaction of Borrelia burgdorferi with Peripheral Blood Fibrocytes, Antigen-Presenting Cells with the Potential for Connective Tissue Targeting. Mol Med 5, 46–54 (1999). https://doi.org/10.1007/BF03402138
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DOI: https://doi.org/10.1007/BF03402138