title: Borrelia burgdorferi clinical isolates induce human innate immune responses that are not dependent on genotype.
abstract: Borrelia burgdorferi can be categorized based on restriction fragment length polymorphism analysis into ribosomal spacer type (RST) 1, 2 and 3. A correlation between RST type and invasiveness of Borrelia isolates has been demonstrated in clinical studies and experimental models, and RST 1 isolates are more likely to cause disseminated disease than RST 3 isolates. We hypothesized that this could partially be due to increased susceptibility of RST 3 isolates to killing by the innate immune system early in infection. Thus, we investigated the interaction of five RST 1 and five RST 3 isolates with various components of the human innate immune system in vitro. RST 3 isolates induced significantly greater upregulation of activation markers in monocyte-derived dendritic cells compared to RST 1 isolates at a low multiplicity of infection. However, RST 1 isolates stimulated greater interleukin-6 production. At a high multiplicity of infection no differences in dendritic cell activation or cytokine production were observed. In addition, we observed no differences in the ability of RST 1 and RST 3 isolates to activate monocytes or neutrophils and all strains were phagocytosed at a comparable rate. Finally, all isolates tested were equally resistant to complement-mediated killing, as determined by dark-field microscopy and a growth inhibition assay. In conclusion, we demonstrate that the RST 1 and 3 isolates showed no distinction in their susceptibility to the various components of the human immune system studied here, suggesting that other factors are responsible for their differential invasiveness.
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands. Electronic address: l.m.mason@amc.uva.nl.
authors.forename: Lauren M K
authors.initials: LM
authors.lastname: Mason
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Eduard A
authors.initials: EA
authors.lastname: Herkes
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Krupna-Gaylord
authors.affiliation: Department of Medical Microbiology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Anneke
authors.initials: A
authors.lastname: Oei
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
authors.affiliation: Division of Infectious Disease, New York Medical College, Valhalla, NY, USA.
authors.forename: Gary P
authors.initials: GP
authors.lastname: Wormser
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA.
authors.forename: Ira
authors.initials: I
authors.lastname: Schwartz
authors.affiliation: Department of Microbiology and Immunology, New York Medical College, Valhalla, NY, USA.
authors.forename: Mary M
authors.initials: MM
authors.lastname: Petzke
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Joppe W R
authors.initials: JW
authors.lastname: Hovius
mesh_terms: D025065:Borrelia burgdorferi / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification; D003165:Complement System Proteins / Q000276:immunology; D005260:Female; D005838:Genotype; D006801:Humans; D007113:Immunity, Innate; D015850:Interleukin-6 / Q000276:immunology*; D008193:Lyme Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6; D003165:Complement System Proteins
keywords: Borrelia; Innate immunity; Lyme