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

  • Eliza Mnich Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.;
  • Adrian Gajewski Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.;
  • Karolina Rudnicka Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.;
  • Weronika Gonciarz Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.;
  • Paweł Stawerski Department of Pathomorphology, Medical University of Łódź, Łódź, Poland.;
  • Krzysztof Hinc Intercollegiate Faculty of Bacteriology UG&MUG, Department of Molecular Bacteriology, Gdańsk, Poland.;
  • Michał Obuchowski Intercollegiate Faculty of Bacteriology UG&MUG, Department of Molecular Bacteriology, Gdańsk, Poland.;
  • Magdalena Chmiela Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.;

Abstract

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 [(3)H]-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.
Published
2015-11-03
Section
Articles