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2015 | 62 | 4 | 641-650
Article title

Immunoregulation of antigen presenting and secretory functions of monocytic cells by Helicobacter pylori antigens in relation to impairment of lymphocyte expansion

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The role of Helicobacter pylori (H. pylori) antigens in driving a specific immune response against the bacteria causing gastroduodenal disorders is poorly understood. Using a guinea pig model mimicking the natural history of H. pylori infection, we evaluated the effectiveness of immature and mature macrophages in promoting the blastogenesis of splenocytes from H. pylori infected and uninfected animals, in response to H. pylori antigens: glycine acid extract (GE), cytotoxin associated gene A protein (CagA), urease A (UreA) and lipopolysaccharide (LPS). Lymphocyte expansion was assessed in 72 h cell cultures, containing: immature or mature macrophages derived from bone marrow monocytes, unstimulated or stimulated with H. pylori antigens for 2 h. The proliferation was expressed as a ratio of [3H]-thymidine incorporation into DNA of antigen-stimulated to unstimulated cells and the DNA damage was determined by DAPI cell staining. TGF-β and IFN-γ were assessed immunoenzymatically in cell culture supernatants. Lymphocytes of control and H. pylori-infected animals proliferated intensively in response to phytohaemagglutinin (PHA) and in co-cultures with immature or mature macrophages treated with CagA or UreA (significantly) and GE (slightly) exluding the cultures containing H. pylori or E. coli LPS. This lymphocyte growth inhibition was related to DNA damage of monocytic cells in response to H. pylori or E. coli LPS and secretion of regulatory TGF-β, but not proinflammatory IFN-γ. Impaired homeostasis of monocytic cell function related to DNA damage and TGF-β release, in response to H. pylori LPS may lead to the suppression of adaptive immune response against the bacteria and development of chronic infection.
Physical description
  • Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland
  • Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland
  • Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland
  • Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland
  • Department of Pathomorphology, Medical University of Łódź, Łódź, Poland
  • Intercollegiate Faculty of Bacteriology UG&MUG, Department of Molecular Bacteriology, Gdańsk, Poland
  • Intercollegiate Faculty of Bacteriology UG&MUG, Department of Molecular Bacteriology, Gdańsk, Poland
  • Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland
  • Bickley J, Owen RJ, Fraser AG, Pounder RE (1993) Evaluation of the polymerase chain reaction for detecting the urease C gene of Helicobacter pylori in gastric biopsy samples and dental plaque. J Med Microbiol 39: 338-344.
  • Blaser MJ, Berg DE (2001) Helicobacter pylori genetic diversity and risk of human disease. J Clin Invest 107: 767-773.
  • Boncristiano M, Paccani SR, Barone S, Ulivieri C, Patrussi L, Ilver D, Amedei A, D'elios MM, Telford JL, Baldari CT (2003) The Helicobacter pylori vacuolating toxin inhibits T cell activation by two independent mechanisms. J Exp Med 198: 1887-1897.
  • Boren T, Falk P, Roth KA, Larson G, Normark S (1993) Attachment of Helicobacter pylori to human gastric epithelium mediated by blood group antigens. Science 262: 1892-1895.
  • Bryn T, Yaqub S, Mahic M, Henjum K, Aandahl EM, Tasken K (2007) LPS-activated monocytes suppress T-cell immune responses and induce FOXP3+T cells through a COX-2-PGE2-dependent mechanism. Int Immunol 20: 235-245.
  • Chmiela M, Michetti P (2006) Inflammation, immunity, vaccines for Helicobacter infection. Helicobacter 11 (suppl.1): 21-26.
  • Chmiela M, Rudnicka K, Miszczyk E (2014) Structural modifications of Helicobacter pylori lipopolysaccharide: an idea for how to live in peace. World J Gastroenterol 20: 9882-9897.
  • Covacci A, Censini S, Bugnoli M, Petracca R, Burroni D, Macchia G, Massone A, Papini E, Xiang Z, Figura N, Rappuoli R (1993) Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer. Proc Natl Acad Sci USA 90: 5791-5795.
  • D'elios MM, Amedei A, Manghetti M, Costa F, Baldari CT, Quazi AS, Telford JL, Romagnani S, Prete G (1999) Impaired T-cell regulation of B-cell growth in Helicobacter pylori-related gastric low-grade MALT lymphoma. Gastroenterology 117: 1105-1112.
  • Dubreuil JD, Giudice GD, Rappuoli R (2002) Helicobacter pylori interactions with host serum and extracellular matrix proteins: potential role in the infectious process. Microbiol Mol Biol Rev 66: 617-629.
  • Dunn BE, Campbell GP, Perez-Perez GI, Blaser MJ (1990) Purification and characterization of urease from Helicobacter pylori. J Biol Chem 265: 9464-9469.
  • Evans DJ Jr, Evans DG (2000) Helicobacter pylori adhesins: review and perspectives. Helicobacter 5: 183-195.
  • Fainaru O, Woolf E, Lotem J, Yarmus M, Brenner O, Goldenberg D, Negreanu V, Bernstein Y, Levanon D, Jung S, Groner Y (2004) Runx3 regulates mouse TGF-beta-mediated dendritic cell function and its absence results in airway inflammation. EMBO J 23: 969-979.
  • Fernandez IE, Eickelberg O (2012) The impact of TGF-β on lung fibrosis: from targeting to biomarkers. Proc Am Thorac Soc 9: 111-116.
  • Grębowska A, Moran AP, Matusiak A, Bak-Romaniszyn L, Czkwianianc E, Rechcinski T, Walencka M, Planeta-Malecka I, Rudnicka W, Chmiela M (2008) Anti-phagocytic activity of Helicobacter pylori lipopolysaccharide (LPS) - possible modulation of the innate immune response to these bacteria. Pol J Microbiol 57: 185-192.
  • Hannon GJ, Beach D (1994) p15INK4B is a potential effector of TGF-beta-induced cell cycle arrest. Nature 371: 257-262.
  • Hinc K, Isticato R, Dembek M, Karczewska J, Iwanicki A, Peszyńska-Sularz G, De Felice M, Obuchowski M, Ricca E (2010) Expression and display of UreA of Helicobacter acinonychis on the surface of Bacillus subtilis spores. Microbial Cell Factories 9: 2.
  • Israel DA, Peek RM (2001) Pathogenesis of H. pylori-induced gastric inflammation. Aliment Pharmacol Ther 15: 1271-1290.
  • Israel DA, Salama N, Arnold CN, Moss SF, Ando T, Wirth HP, Tham KT, Camorlinga M, Blaser MJ, Falkow S, Peek RM Jr (2001) Helicobacter pylori strain-specific differences in genetic content, identified by microarray, influence host inflammatory responses. J Clin Invest 107: 611-620.
  • Johansen HK, Norgaard A, Andersen L, Jensen P, Nielsen H, Hoiby N (1995) Cross-reactive antigens shared by Pseudomonas aeruginosa, Helicobacter pylori, Campylobacter jejuni, and Haemophilus influenzae may cause false-positive titres of antibody to H. pylori. Clin Diagn Lab Immunol 2: 149-155.
  • Labigne A, Cussac V, Courcoux P (1991) Shuttle cloning and nucleotide sequences of Helicobacter pylori genes responsible for urease activity. J Bacteriol 173: 1920-1931.
  • Marshall BJ (2001) One hundred years of discovery and rediscovery of Helicobacter pylori and its association with peptic ulcer disease. In: Mobley HLT, Mendez GL, Hazell SL, editors. Helicobacter pylori: Physiology and Genetics. Washington (DC). ASM Press, Chapter 3. pp 19-24.
  • Massague J, Blain SW, Lo RS (2000) TGF-β signalling in growth control, cancer, and heritable disorders. Cell 103: 295-309.
  • Miszczyk E, Walencka M, Rudnicka K, Matusiak A, Rudnicka W, Chmiela M (2014) Antigen-specific lymphocyte proliferation as a marker of immune response in guinea pigs with sustained Helicobacter pylori infection. Acta Biochim Pol 61: 295-303.
  • Monks J, Rosner D, Geske FJ, Lehman L, Hanson L, Neville MC, Fadok VA (2005) Epithelial cells as phagocytes: apoptotic epithelial cells are engulfed by mammary alveolar epithelial cells and repress inflammatory mediator release. Cell Death Differ 12: 107-114.
  • Moran AP, Helander IM, Kosunen TU (1992) Compositional analysis of Helicobacter pylori rough-form lipopolysaccharides. J Bacteriol 174: 1370-1377.
  • Nguyen DN, Jiang P, Jacobsen S, Sangild PT, Bendixen E, Chatterton DE (2015) Protective effects of transforming growth factor β2 in intestinal epithelial cells by regulation of proteins associated with stress and endotoxin responses. PLOS ONE 10: e0117608.
  • Portal-Celhay C, Perez-Perez GI (2006) Immune responses to Helicobacter pylori colonization: mechanisms and clinical outcomes. Clin Sci (Lond) 110: 305-314.
  • Quiding-Jarbrink M, Ahlstedt I, Lindholm C, Johansson EL, Lönroth H (2001) Homing commitment of lymphocytes activated in the human gastric and intestinal mucosa. Gut 49: 519-525.
  • Rain JC, Selig L, De Reuse H, Battaglia V, Reverdy C, Simon S, Lenzen G, Petel F, Wojcik J, Schächter V, Chemama Y, Labigne A, Legrain P (2001) The protein-protein interaction map of Helicobacter pylori. Nature 409: 211-215.
  • Rechciński T, Chmiela M, Małecka-Panas E, Płaneta-Małecka I, Rudnicka W (1997) Serological indicators of Helicobacter pylori infection in adult dyspeptic patients and healthy blood donors. Microbiol Immunol 41: 387-393.
  • Rudnicka W, Jarosinska A, Bak-Romaniszyn L, Moran A, Planeta-Malecka I, Wadstrom T, Chmiela M (2003) Helicobacter pylori lipopolysaccharide in the IL-2 milieu activates lymphocytes from dyspeptic children. FEMS Immunol Med Microbiol 36: 141-145.
  • Rudnicka K, Miszczyk E, Matusiak A, Walencka M, Moran AP, Rudnicka W, Chmiela M (2015) Helicobacter pylori-driven modulation of NK cell expansion, intracellular cytokine expression and cytotoxic activity. Innate Immun 21: 127-139.
  • Rudnicka K, Włodarczyk M, Moran AP, Rechciński T, Miszczyk E, Matusiak A, Szczęsna E, Walencka M, Rudnicka W, Chmiela M (2012) Helicobacter pylori antigens as potential modulators of lymphocyes' cytotoxic activity. Microbiol Immunol 56: 62-75.
  • Suzuki R, Shiota S, Yamaoka Y (2012) Molecular epidemiology, population genetics, and pathogenic role of Helicobacter pylori. Infect Genet Evol 12: 203-213.
  • Versalovic J (2003) Helicobacter pylori. Pathology and diagnostic strategies. Am J Clin Pathol 119: 403-412.
  • Wallet MA, Sen P, Tisch R (2005) Immunoregulation of dendritic cells. Clin Med Res 3: 166-175.
  • Wessler S and Backert S (2008) Molecular mechanisms of epithelial-barrier disruption by H. pylori. Trends Microbiol 16: 397-405.
  • Wiśniewska M, Nilsson HO, Bąk-Romaniszyn L, Rechciński T, Bielański W, Płaneta-Małecka I, Płonka M, Konturek S, Wadström T, Rudnicka W, Chmiela M (2002) Detection of specific H. pylori DNA and antigens in stool samples in dyspeptic patients and healthy subjects. Microbiol Immunol 46: 657-665.
  • Wolk K, Döcke WD, von Baehr V, Volk HD, Sabat R (2000) Impaired antigen presentation by human monocytes during endotoxin tolerance. Blood 96: 218-223.
  • Xiuying Du (2013) On coupling analysis of complex network and pathogenesis dynamics of gastroduodenal disease. Inf Technol J 12: 429-433.
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