RESEARCH PAPER
Synthesis of Th17 cytokines in the culture of peripheral blood mononuclear cells stimulated with Borrelia burgdorferi sensu lato
 
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Department of Infectious Diseases and Neuroinfections, Medical University, Białystok, Poland
 
 
Corresponding author
Sambor Grygorczuk   

Department of Infectious Diseases and Neuroinfections, Medical University, Białystok, Poland
 
 
Ann Agric Environ Med. 2016;23(2):242-247
 
KEYWORDS
ABSTRACT
Introduction and objective:
Th17 lymphocytes and their cytokines, interleukin 17A (IL-17A), IL-17F and IL-22, participate in the response to extracellular bacteria and in the autoimmunity and may be engaged in the pathogenesis of Lyme borreliosis. Concentrations were measured of IL-17A, IL-17F and IL-22 in the supernatant of the peripheral blood mononuclear cells (PBMC) culture stimulated with Borrelia burgdorferi sensu lato (B. burgdorferi).

Material and Methods:
The study group consisted of 13 patients with early disseminated and late Lyme borreliosis and a control group of 7 healthy persons. PBMC cultures were stimulated for 48 hours with B. burgdorferi spirochetes of three pathogenic species: B. burgdorferi sensu stricto, B. afzelii or B. garinii, in the multiplicity of infection 10:1. Concentrations of Th17 cytokines IL-17A, IL-17F and IL-22, as well as Th2/immunoregulatory cytokine IL-10 were measured with ELISA assays.

Results:
Expression of IL-17A, IL-17F and IL-22 increased under stimulation, simultaneously with the increased IL-10 expression. Concentration of IL-17F tended to be lower in early neuroborreliosis than in late Lyme borreliosis and than in controls. B. afzelii elicited higher expression of IL-17A than the other two species.

Conclusions:
IL-17A, IL-17F and IL-22 are synthesized simultaneously by PBMC stimulated with B. burgdorferi. There is no antagonism between Th17 response and IL-10 expression. The role of Th17 cytokines seems to differ depending on the clinical stage of Lyme borreliosis and on the B. burgdorferi species.

 
REFERENCES (22)
1.
Steere AC, Klitz W, Drouin EE, Falk BA, Kwok WW, Nepom GT, et al. Antibiotic-refractory Lyme arthritis is associated with HLA-DR molecules that bind a Borrelia burgdorferi peptide. J Exp Med. 2006; 203(4): 961–971.
 
2.
Shin JJ, Glickstein LJ, Steere AC. High levels of inflammatory chemokines and cytokines in joint fluid and synovial tissue throughout the course of antibiotic-refractory Lyme arthritis. Arthritis Rheum. 2007; 56(4): 1325–1335.
 
3.
Shen S, Shin JJ, Strle K, McHugh G, Li X, Glickstein LJ et al. T regulatory cell number and function in patients with antibiotic-refractory and antibiotic-responsive Lyme arthritis. Arthritis Rheum. 2010; 62(7): 2127–2137.
 
4.
Strle K, Stupica D, Drouin EE, Steere AC, Strle F. Elevated levels of IL-23 in a subsets of patients with post-Lyme disease symptoms following erythema migrans. Clin Infect Dis. 2014; 58(3): 372–380.
 
5.
Strle K, Drouin EE, Shen S, Khoury JE, McHugh G, Ružić-Sabljić E et al. Borrelia burgdorferi stimulates macrophages to secrete higher levels of cytokines and chemokines than Borrelia afzelii or Borrelia garinii. J Infect Dis. 2009; 200(12): 1936–1943.
 
6.
Infante-Duarte C, Horton HF, Byrne MC, Kamradt T. Microbial lipopeptides induce the production of IL-17 in Th cells. J Immunol. 2000; 165(11): 6107–6115.
 
7.
Gaffen SL. An overview of IL-17 function and signaling. Cytokine 2008; 43(3): 402–407.
 
8.
Nistala K, Moncrieffe H, Newton KR, Varsani H, Hunter P, Wedderburn LR. Interleukin-17-producing T cells are entiched in the joints of children with arthritis, but have a reciprocal relationship to regulatory T cell numbers. Arthritis Rheum. 2008; 58(3): 875–887.
 
9.
Eyerich S, Eyerich K, Cavani A, Schmidt-Weber C. IL-17 and IL-22: siblings, not twins. Trends Immunol. 2010; 31(9): 354–361.
 
10.
Chabaud M, Durand JM, Buchs N, Fossiez F, Page G, Frappart L et al. Human interleukin-17. A T cell-derived proinflammatory cytokine produced by the rheumatoid synovium. Arthritis Rheum. 1999; 42(5): 963–970.
 
11.
Nardelli DT, Kevin Luk KH, Kotlosky NJ, Warmer TF, Torrealba JR et al. Role of IL-17, transforming growth factor-beta, and IL-6 in the development of arthritis and production of anti-outer surface protein A borreliacidal antibodies in Borrelia-vaccinated and –challenged mice. FEMS Immunol Med Microbiol. 2008; 53(2): 265–274.
 
12.
Zrioual S, Ecochard R, Tournadre A, Lenief V, Cazalis MA, Miossec P. Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes. J Immunol. 2009; 182(5): 3112–3120.
 
13.
Bachmann M, Horn K, Rudloff I, Goren I, Holdener M, Christen U et al. Early production of IL-22 but not IL-17 by peripheral blood mononuclear cells exposed to live Borrelia burgdorferi: the role of monocytes and interleukin-1. PLoS Pathogens 2010; 6(10): e1001144.
 
14.
Henningsson AJ, Tjernberg I, Malmvall B-E, Forsberg P, Ernerudh J. Indications of Th1 and Th17 responses in cerebrospinal fluid from patients with Lyme neuroborreliosis: a large retrospective study. J Neuroinflam. 2011; 8: 36–46.
 
15.
Nordberg M, Forsberg P, Johansson A, Nyman D, Jansson Ch, Ernerudh J et al. Cytotoxic mechanisms may play role in the local immune response in the central nervous system in neuroborreliosis. J Neuroimmunol. 2011; 232(1–2): 186–193.
 
16.
Matusevicius D, Kivisäkk P, He B, Kostulas N, Özenci V, Fredrikson S et al. Interleukin-17 mRNA expression in blood and CSF mononuclear cells is augmented in multiple sclerosis. Multiple Sclerosis 1999; 5(2): 101–104.
 
17.
Genovese MC, van den Bosch F, Robertson A, Bojin S, Biagini IM, Ryan P et al. LTY2439821, a humanized anti-interleukin-17 monoclonal antibody, in the treatment of patients with rheumatoid arthritis. A phase I randomized, double blind, placebo-controlled, proof-of-concept study. Arthritis Rheum. 2010(4); 62; 929–39.
 
18.
Lubberts E. Th17 cytokines and arthritis. Semin Immunopathol. 2010; 32(1): 43–53.
 
19.
Kotloski NJ, Nardelli DT, Peterson SH, Torrealba JR, Warner TF, Callister SM et al. Interleukin-23 is required for development of arthritis in mice vaccinated and challenged with Borrelia species. Clin Vaccine Immunol. 2008; 15(8): 1199–1207.
 
20.
Janský L, Reymanová P, Kopecký J. Dynamics of cytokine production in human peripheral blood mononuclear cells stimulated by LPS or infected by Borrelia. Physiol Res. 2003; 52(6): 593–598.
 
21.
Henningsson AJ, Malmvall B-E, Ernerudh J, Matussek A, Forsberg P. Neuroborreliosis – an epidemiological, clinical and healthcare cost study from an endemic area in the south-east of Sweden. Clin Microbiol Infect. 2010; 16(8): 1245–1251.
 
22.
Wilske B, Fingerle V, Schulte-Spechtel U. Microbiological and serological diagnosis of Lyme borreliosis. FEMS Immunol Med Microbiol. 2007; 49(1): 13–21.
 
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ISSN:1232-1966
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