ASSOCIATION OF MACROPHAGE INFLAMMATORY RESPONSE AND CELL DEATH AFTER IN VITRO BORRELIA BURGDORFERI INFECTION WITH ARTHRITIS RESISTANCE

Susceptibility to Borrelia burgdorferi infection and subsequent arthritis is genetically determined in mice and determined by innate immunity. Accordingly, macrophage responses to B. burgdorferi challenge may differ between mouse strains. Bone marrow-derived macrophages were infected ex vivo with clonal B. burgdorferi strain N40. Interleukin-12 and tumor necrosis factor-alpha (TNF-alpha) production were higher in macrophages from resistant C57Bl/6 mice than in macrophages from susceptible C3H/HeJ mice. However, TNF-alpha production was observed in lower concentrations in C3H/HeJ (toll-like receptor-4(-/-)) macrophages than in C3H/FeJ (TLR4(+/+)) macrophages, suggesting that TLR4 might contribute to the response to B. burgdorferi. A higher cytokine response to B. burgdorferi was associated with cell death in macrophages from resistant C57Bl/6 mice. Understanding variability in the response of macrophages to B. burgdorferi may contribute to understanding Lyme arthritis.

[1]  G. F. Weber,et al.  Borrelia burgdorferi, an extracellular pathogen, circumvents osteopontin in inducing an inflammatory cytokine response , 2005, Journal of leukocyte biology.

[2]  M. Amicosante,et al.  Proinflammatory cytokines in the course of Mycobacterium tuberculosis-induced apoptosis in monocytes/macrophages. , 2002, The Journal of infectious diseases.

[3]  M. Kubo,et al.  SOCS1/JAB is a negative regulator of LPS-induced macrophage activation. , 2002, Immunity.

[4]  M. Widhe,et al.  Increased expression of the Th1-inducing cytokines interleukin-12 and interleukin-18 in cerebrospinal fluid but not in sera from patients with Lyme neuroborreliosis , 2002, Journal of Neuroimmunology.

[5]  J. Weis,et al.  Host-pathogen interactions and the pathogenesis of murine Lyme disease. , 2002, Current opinion in rheumatology.

[6]  Jeffrey Talkington,et al.  Role of Fc Gamma Receptors in Triggering Host Cell Activation and Cytokine Release by Borrelia burgdorferi , 2001, Infection and Immunity.

[7]  S. Bodary,et al.  Characterization of a candidate Borrelia burgdorferiβ3‐chain integrin ligand identified using a phage display library , 1999, Molecular microbiology.

[8]  R. Doerge,et al.  Identification of quantitative trait loci governing arthritis severity and humoral responses in the murine model of Lyme disease. , 1999, Journal of immunology.

[9]  C. Teuscher,et al.  Distinct Characteristics of Resistance toBorrelia burgdorferi-Induced Arthritis in C57BL/6N Mice , 1998, Infection and Immunity.

[10]  M. Mbow,et al.  Effects of Ixodes scapularis and Borrelia burgdorferi on modulation of the host immune response: induction of a TH2 cytokine response in Lyme disease-susceptible (C3H/HeJ) mice but not in disease-resistant (BALB/c) mice , 1997, Infection and immunity.

[11]  Ruth R. Montgomery,et al.  Entry of Borrelia burgdorferi into macrophages is end-on and leads to degradation in lysosomes , 1996, Infection and Immunity.

[12]  R. Gazzinelli,et al.  Effects of IL-12 on immune responses to microbial infections: a key mediator in regulating disease outcome. , 1995, Current opinion in immunology.

[13]  B. Huber,et al.  Karoushi--death by overwork in the immune system. , 1995, Journal of immunology.

[14]  L. Davis,et al.  Treponema pallidum and Borrelia burgdorferi lipoproteins and synthetic lipopeptides activate monocytes/macrophages. , 1995, Journal of immunology.

[15]  D. Persing,et al.  Heritable susceptibility to severe Borrelia burgdorferi-induced arthritis is dominant and is associated with persistence of large numbers of spirochetes in tissues , 1994 .

[16]  M. de Souza,et al.  Chronic Lyme borreliosis in the laboratory mouse. , 1993, The American journal of pathology.

[17]  J. Coburn,et al.  Integrin alpha IIb beta 3 mediates binding of the Lyme disease agent Borrelia burgdorferi to human platelets. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[18]  S. Barthold,et al.  Lyme borreliosis in genetically resistant and susceptible mice with severe combined immunodeficiency. , 1992, The American journal of tropical medicine and hygiene.

[19]  R. C. Johnson,et al.  In vitro and in vivo induction of tumor necrosis factor alpha by Borrelia burgdorferi , 1992, Infection and immunity.

[20]  U. Schaible,et al.  Experimental Borrelia burgdorferi infection in inbred mouse strains: Antibody response and association of H‐2 genes with resistance and susceptibility to development of arthritis , 1991, European journal of immunology.

[21]  J. Coburn,et al.  Integrin CqIbP3 mediates binding of the Lyme disease agent Borrelia burgdorferi to human platelets , 2005 .

[22]  D. Fish,et al.  Suppression of Acute Ixodes scapularis-Induced Borrelia burgdorferi Infection using Tumor Necrosis Factor-α, Interleukin-2, and Interferon-γ , 1996 .

[23]  D. Fish,et al.  Suppression of acute Ixodes scapularis-induced Borrelia burgdorferi infection using tumor necrosis factor-alpha, interleukin-2, and interferon-gamma. , 1996, The Journal of infectious diseases.

[24]  D. Persing,et al.  Heritable susceptibility to severe Borrelia burgdorferi-induced arthritis is dominant and is associated with persistence of large numbers of spirochetes in tissues. , 1994, Infection and immunity.