title: Increased expression of Fas receptor and Fas ligand in the culture of the peripheral blood mononuclear cells stimulated with Borrelia burgdorferi sensu lato.
abstract: Apoptosis of the lymphocytes plays an essential role in the regulation of inflammatory/immune responses and its abnormalities may contribute to a chronic infection, persistent inflammation and autoimmunity. Its role in the pathogenesis of the late Lyme borreliosis manifestations has not been studied so far. We have measured Th lymphocyte apoptosis rate, membrane expression of pro-apoptotic Fas receptor, and supernatant concentrations of selected soluble pro- and anti-apoptotic mediators in cultures of peripheral blood mononuclear cells from 16 patients with disseminated Lyme borreliosis (6 with osteoarticular symptoms, 7 with neuroborreliosis and 3 with acrodermatitis chronica atrophicans) and 8 healthy controls. The cultures stimulated for 48h with live Borrelia burgdorferi sensu stricto, B. garinii or B. afzelii spirochetes. Fraction of the apoptotic Th (CD3+CD4+) lymphocytes and expression of Fas in this cell population was measured cytometrically and concentrations of soluble Fas, soluble Fas ligand, IL-10, IL-12 and TGF-β in culture supernatant with ELISA assays. The expression of IL-10, soluble and membrane Fas and soluble Fas ligand was increased under stimulation and higher in the presence of B. burgdorferi sensu stricto than the other species. Apoptosis rate was not affected. There was no difference between Lyme borreliosis patients and controls. IL-10 concentration correlated negatively with the membrane Fas expression and apoptosis under stimulation with B. afzelii and B. garinii. Expression of Fas/FasL system is up-regulated under stimulation with B. burgdorferi, but without corresponding increase in lymphocyte apoptosis. Variable responses observed with different B. burgdorferi species may reflect differences in the pathogenesis of the infection in vivo.
authors.affiliation: Department of Infectious Diseases and Neuroinfections, Medical University in Białystok, ul. Żurawia 14, 15-540 Białystok, Poland. Electronic address: grygorczuk.sambor@neostrada.pl.
authors.forename: Sambor
authors.initials: S
authors.lastname: Grygorczuk
authors.affiliation: Department of Hematologic Diagnostics, Medical University in Białystok, ul. Waszyngtona 15A, 15-269 Białystok, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Osada
authors.affiliation: Department of Infectious Diseases and Neuroinfections, Medical University in Białystok, ul. Żurawia 14, 15-540 Białystok, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Moniuszko
authors.affiliation: Department of Infectious Diseases and Neuroinfections, Medical University in Białystok, ul. Żurawia 14, 15-540 Białystok, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Świerzbińska
authors.affiliation: Department of Infectious Diseases and Neuroinfections, Medical University in Białystok, ul. Żurawia 14, 15-540 Białystok, Poland.
authors.forename: Maciej
authors.initials: M
authors.lastname: Kondrusik
authors.affiliation: Department of Infectious Diseases and Neuroinfections, Medical University in Białystok, ul. Żurawia 14, 15-540 Białystok, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Zajkowska
authors.affiliation: Department of Infectious Diseases and Neuroinfections, Medical University in Białystok, ul. Żurawia 14, 15-540 Białystok, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Dunaj
authors.affiliation: Department of Hematologic Diagnostics, Medical University in Białystok, ul. Waszyngtona 15A, 15-269 Białystok, Poland.
authors.forename: Milena
authors.initials: M
authors.lastname: Dąbrowska
authors.affiliation: Department of Infectious Diseases and Neuroinfections, Medical University in Białystok, ul. Żurawia 14, 15-540 Białystok, Poland.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Pancewicz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis; D001899:Borrelia Infections / Q000276:immunology* / Q000378:metabolism; D025065:Borrelia burgdorferi / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism*; D053222:Fas Ligand Protein / Q000378:metabolism*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008193:Lyme Disease / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D016207:Cytokines; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C508609:IL10 protein, human; D016212:Transforming Growth Factor beta; D019014:fas Receptor; D016753:Interleukin-10; D018664:Interleukin-12
keywords: Fas receptor; Lyme borreliosis; Lymphocyte activation; Lymphocyte apoptosis