Anti-phagocytic activity of Helicobacter pylori lipopolysaccharide (LPS)--possible modulation of the innate immune response to these bacteria (original) (raw)
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Immunomodulating Effect of Lipopolysaccharide (LPS) Isolated From Virulent Strains of H.Pylori
Microbiology & Infectious Diseases
The mechanism by which Helicobacter pylori, which has little or no invasive activity, induces gastric-tissue inflammation and injury has not been well characterized. Extensive research during the past 2 decades has revealed the mechanism by which continued oxidative stress can lead to chronic inflammation, which in turn could mediate most chronic diseases including gastritis. The present study is aimed to analyze the effect of H pylori Lipopolysaccharide LPS on immune system activation particularly oxidative stress. We have investigated the immunomodulatory effect of H. pylori LPS isolated from gastritis patients. LPS was challenged to neutrophils and macrophage, in response to which reactive oxygen species (ROS) and reactive nitrogen species (NO) were measured by chemiluminescence technique and spectrophotometry respectively. Additionally effect on T-cells proliferation was also studied by radioactive thymidine incorporation using scintillation counter. In this study, we have found that out of 10 different samples of H. Pylori LPS, 6 of the LPS samples resulted in 2-6 µM of NO nitric oxide production in vitro. About 3 samples were aggravating reactive oxygen species production and almost all the samples moderately inhibited proliferation of T cell. All these events modulated by LPS clearly indicating the role of bacterial lipopolysaccharide in an increased proinflammatory activity which may lead to gastritis.
Journal of Clinical Investigation, 1991
The inflammatory lesions associated with Helicobacter pylori gastritis and duodenitis contain large numbers of mononuclear cells. The close proximity of H. pylori to gastric mucosa suggests that the organism interacts with mononuclear cells, thereby modulating the inflammatory response. To investigate the role of monocytes/macrophages in this response, we examined the effect of whole H. pylori bacteria, H. pylori surface proteins, and H. pylori lipopolysaccharide (LPS) on purified human monocytes. Whole H. pylori and the extracted LPS induced expression of the monocyte surface antigen HLA-DR and interleukin-2 receptors, production of the inflammatory cytokines interleukin 1 and tumor necrosis factor (peptide and messenger RNA), and secretion of the reactive oxygen intermediate superoxide anion. Since H. pylori in vivo does not invade mucosal tissue, we determined whether soluble constituents of the bacteria could activate monocytes. Soluble H. pylori surface proteins, which are enriched for urease and do not contain LPS, stimulated phenotypic, transcriptional, and functional changes consistent with highly activated monocytes.
PubMed, 2010
Helicobacter pylori (H. pylori) have been recognized as a major cause of chronic gastritis, gastric and duodenal ulcers and gastric cancer. Macrophages are the targets of lipopolysaccharide (LPS), which is a constituent of the outer membrane of Gram-negative rods. In this study we focused on a potential role of macrophages in the proliferation of human peripheral blood mononuclear leukocytes (PBML) in the milieu of H. pylori LPS and standard E. coli LPS. First, we found that H. pylori and E. coli LPS induced proliferation of total PBML (tPBML) from 5 out 21 healthy blood donors (LPS responders). In the LPS milieu, tPBML from the majority of volunteers (LPS non-responders) showed a significant decrease in the [(3)H]-thymidine incorporation as compared to tPBML in medium alone. The decreased cell proliferation was associated with a diminished metabolic activity of non-adherent lymphocytes. Then, non-adherent lymphocytes were stimulated with autologous macrophages pulsed with bacterial LPS. Still, the lymphocytes from the non-responders did not proliferate in the cultures with LPS exposed macrophages. In the group of LPS responders, the macrophages pulsed with H. pylori LPS significantly reduced the proliferation of non-adherent lymphocytes. The possible mechanism regulating the responses of PBML to bacterial LPS with an implication for the outcome of H. pylori infections is discussed.
Helicobacter, 2010
Background: Helicobacter pylori infection can lead to the development of gastritis, peptic ulcers and gastric cancer, which makes this bacterium an important concern for human health. Despite evoking a strong immune response in the host, H. pylori persists, requiring complex antibiotic therapy for eradication. Here we have studied the impact of a patient’s immune serum on H. pylori in relation to macrophage uptake, phagosome maturation, and bacterial killing.Materials and Methods: Primary human macrophages were infected in vitro with both immune serum-treated and control H. pylori. The ability of primary human macrophages to kill H. pylori was characterized at various time points after infection. H. pylori phagosome maturation was analyzed by confocal immune fluorescence microscopy using markers specific for H. pylori, early endosomes (EEA1), late endosomes (CD63) and lysosomes (LAMP-1).Results: Immune serum enhanced H. pylori uptake into macrophages when compared to control bacteria. However, a sufficient inoculum remained for recovery of viable H. pylori from macrophages, at 8 hours after infection, for both the serum-treated and control groups. Both serum-treated and control H. pylori phagosomes acquired EEA1 (15 minutes), CD63 and LAMP-1 (30 minutes). These markers were then retained for the rest of an 8 hour time course.Conclusions: While immune sera appeared to have a slight positive effect on bacterial uptake, both serum-treated and control H. pylori were not eliminated by macrophages. Furthermore, the same disruptions to phagosome maturation were observed for both serum-treated and control H. pylori. We conclude that to eliminate H. pylori, a strategy is required to restore the normal process of phagosome maturation and enable effective macrophage killing of H. pylori, following a host immune response.
Mediators of Inflammation, 2014
The immune response toHelicobacter pyloriimportantly determines the pathogenesis of infection as well as the success of antibiotic eradication of the bacteria. Strains ofH. pyloriwere gathered from 14 patients who failed to eradicateH. pyloriinfection with antibiotics—therapy resistant strains (TRS)—or from patients who were able to eradicateH. pyloriinfection—therapy susceptible strains (TSS). The THP-1 cells were stimulated withH. pyloriantigens. Cathepsin X expression on THP-1 cells and concentration of cytokines in the supernatant of THP-1 cells were measured with a flow cytometer. TSSH. pyloriantigens increased the proportion of cathepsin X positive cells compared to TRSH. pyloriantigens. TSSH. pyloriantigens induced higher secretion of IL-12 and IL-6 compared to TRSH. pyloriantigens (P<0.001; 0.02). Polymyxin B, a lipid A inhibitor, lowered the secretion of IL-12 and IL-6 in TRS and TSS. We demonstrated aH. pyloristrain-dependent cathepsin X and cytokine expression that can...
Helicobacter pylori antigens as potential modulators of lymphocytes’ cytotoxic activity
Microbiology and Immunology, 2012
The decrease in lymphocyte cytotoxicity in response to H.p LPS correlated with a lack of IL-2 and IL-12 production, inhibition of interferon-γ production, and low IL-10 secretion by mononuclear leukocytes. IL-12 significantly enhanced the natural as well as H.p LPS and H.p GE driven cytotoxic capacity of lymphocytes. In conclusion, H.p LPS may negatively modulate natural cytotoxic activity and cytokine secretion by immunocompetent cells and thus be involved in the maintenance of infection and development of gastric pathologies.
Mechanisms involved in Helicobacter pylori—Induced inflammation
Gastroenterology, 1993
Back&ound: Helicobacter pylori infection is associated with mucosai inflammation. The aims of the present study were to assess whether a water extract of H. pylori promotes neutrophil (polymorphonuclear leukocyte [PMN]) adherence to endotheliai cells and define the molecular basis of this adhesive interaction. Methods: lntravitai microscopy was used to study leukocyte adhesive interactions in rat mesenteric venules in situ. PMN-endothelial ceil adhesive interactions were studied in vitro using human PMNs and monolayers of human umbilical vein endotheiiai ceils (HUVEC). Results: In vivo, superfusion of rat mesentery with the H. pyloriextract increased leukocyte adhesion and emigration in venules. In vitro, adhesion of human PMNs to HUVEC was increased by the H. pylori extract in a concentration-dependent manner. Pretreatment of HUVEC atone with H. py/ori extract had no effect on PMN adherence, whereas pretreatment of PMN alone significantly increased their adherence to HUVEC. The extract-induced adhesion was significantly diminished by monoclonal antibodies (MAb) directed against either CD1 la, CD1 1 b, or CD18 on neutrophiis, and by MAbs against intercellular adhesion molecule-l (ICAM-l), but not Eor P-selectin, on endotheliai cells. Conclusions: These studies suggest that products of H. pylori elicit gastrointestinal infiammation by promoting PMN adhesion to endothelial ceils via CDlla/CD18-and CDllb/ CD 18-dependent interactions with ICAM-1.
Journal of medical microbiology, 2002
Helicobacter pylori infection in man is associated with chronic gastritis and peptic ulcer disease. The virulence factors of the species are still under investigation. Among these, the lipopolysaccharide (LPS) is a potential pathogenic factor of the micro-organism, whose biological activity can be estimated by immunological parameters. The aim of this study was to determine the ability of pure LPS extracted from clinical isolates of H. pylori to induce mitogenicity, secretion of tumour necrosis factor-alpha (TNF-alpha), and spleen growth in a murine model. Rough and smooth LPS from Salmonella typhimurium were used as controls. The results showed that, like the control LPS, all extracts of LPS induced mitogenic activity, stimulated synthesis of TNF-alpha and induced spleen growth, although the effects produced by the majority of the H. pylori LPS samples analysed were less intensive than those produced by the S. typhimurium LPS. The immunological parameters analysed allowed the detec...