title: Role of Fc gamma receptors in triggering host cell activation and cytokine release by Borrelia burgdorferi.
abstract: Borrelia burgdorferi, the spirochetal bacterium that causes human Lyme disease, encodes numerous lipoproteins which have the capacity to trigger the release of proinflammatory cytokines from a variety of host cell types, and it is generally believed that these cytokines contribute to the disease process in vivo. We previously reported that low-passage-number infectious B. burgdorferi spirochetes express a novel lipidation-independent activity which induces secretion of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) by the mouse MC/9 mast cell line. Using RNase protection assays, we determined that mast cells exposed in vitro to low-passage-number, but not high-passage-number, B. burgdorferi spirochetes show increased expression of additional mRNAs representing several chemokines, including macrophage-inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, and TCA3, as well as the proinflammatory cytokine interleukin-6. Furthermore, mast cell TNF-alpha secretion can be inhibited by the phosphatidylinositol 3-kinase inhibitor wortmannin and also by preincubation with purified mouse immunoglobulin G1 (IgG1) and IgG2a, but not mouse IgG3, and by a mouse Fc gamma receptor II and III (FcgammaRII/III)-specific rat monoclonal antibody, suggesting the likely involvement of host FcgammaRIII in B. burgdorferi-mediated signaling. A role for passively adsorbed rabbit or bovine IgG or serum components in B. burgdorferi-mediated FcgammaR signaling was excluded in control experiments. These studies confirm that low-passage-number B. burgdorferi spirochetes express a novel activity which upregulates the expression of a variety of host cell chemokine and cytokine genes, and they also establish a novel antibody-independent role for FcgammaRs in transduction of activation signals by bacterial products.
authors: Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131, USA.
authors: J
authors: J
authors: Talkington
authors: S P
authors: SP
authors: Nickell
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015748:Borrelia burgdorferi Group / Q000502:physiology*; D002417:Cattle; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D005786:Gene Expression Regulation; D007074:Immunoglobulin G / Q000276:immunology; D018950:Lipopolysaccharide Receptors / Q000502:physiology; D008407:Mast Cells / Q000502:physiology; D051379:Mice; D011817:Rabbits; D017452:Receptors, IgG / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D016207:Cytokines; D007074:Immunoglobulin G; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; D014409:Tumor Necrosis Factor-alpha; D000077191:Wortmannin