title: Immunoregulation of antigen presenting and secretory functions of monocytic cells by Helicobacter pylori antigens in relation to impairment of lymphocyte expansion.
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.
authors.affiliation: Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.
authors.forename: Eliza
authors.initials: E
authors.lastname: Mnich
authors.affiliation: Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Gajewski
authors.affiliation: Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Rudnicka
authors.affiliation: Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.
authors.forename: Weronika
authors.initials: W
authors.lastname: Gonciarz
authors.affiliation: Department of Pathomorphology, Medical University of Łódź, Łódź, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Stawerski
authors.affiliation: Intercollegiate Faculty of Bacteriology UG&MUG, Department of Molecular Bacteriology, Gdańsk, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Hinc
authors.affiliation: Intercollegiate Faculty of Bacteriology UG&MUG, Department of Molecular Bacteriology, Gdańsk, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Obuchowski
authors.affiliation: Division of Gastroimmunology, Department of Immunology and Infectious Biology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Chmiela
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D000942:Antigens, Bacterial / Q000276:immunology*; D018920:Coculture Techniques; D004249:DNA Damage; D016480:Helicobacter pylori / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D051379:Mice; D009000:Monocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D016212:Transforming Growth Factor beta; D007371:Interferon-gamma