Anthony P. Moran

Background: Lipopolysaccharide (LPS) of Helicobacter pylori (Hp) bacteria causes disintegration of gastric tissue cells in vitro. It has been suggested that interleukin (IL)-33 is involved in healing gastric injury. Aim: To elucidate whether Hp LPS affects regeneration of gastric barrier initiated by IL-33. Methods: Primary gastric epithelial cells or fibroblasts from Caviae porcellus were transfected with siRNA IL-33. Such cells, not exposed or treated with LPS Hp, were sub-cultured in the medium with or without exogenous IL-33. Then cell migration was assessed in conjunction with oxidative stress and apoptosis, activation of extracellular signal-regulated kinase (Erk), production of collagen I and soluble ST2 (IL-33 decoy). Results: Control cells not treated with LPS Hp migrated in the presence of IL-33. The pro-regenerative activity of IL-33 was related to stimulation of cells to collagen I production. Wound healing by cells exposed to LPS Hp was inhibited even in the presence of IL-33. This could be due to increased oxidative stress and apoptosis in conjunction with Erk activation, sST2 elevation and modulation of collagen I production. Conclusions: The recovery of gastric barrier cells during Hp infection potentially can be affected due to downregulation of pro-regenerative activity of IL-33 by LPS Hp.

Background: Campylobacter jejuni is a major bacterial cause of food-borne enteritis, and its lipooligosaccharide (LOS) plays an initiating role in the development of the autoimmune neuropathy, Guillain-Barré syndrome, by induction of anti-neural cross-reactive antibodies through ganglioside molecular mimicry. Results: Herein we describe the existence and heterogeneity of multiple LOS forms in C. jejuni strains of human and chicken origin grown at 37°C and 42°C, respectively, as determined on sodium dodecyl sulphate-polyacrylamide electrophoresis gels with carbohydrate-specific silver staining and blotting with anti-ganglioside ligands, and confirmed by nuclear magnetic resonance (NMR) spectroscopy. The C. jejuni NCTC 11168 original isolate (11168-O) was compared to its genome-sequenced variant (11168-GS), and both were found to have a lower-M_r LOS form, which was different in size and structure to the previously characterized higher-M_r form bearing GM₁ mimicry. The lower-M_r form production was found to be dependent on the growth temperature as the production of this form increased from ~5%, observed at 37°C to ~35% at 42°C. The structure of the lower-M_r form contained a β-D-Gal-(1→3)-β-D-GalNAc disaccharide moiety which is consistent with the termini of the GM₁, asialo-GM₁, GD₁, GT₁ and GQ₁ gangliosides, however, it did not display GM₁ mimicry as assessed in blotting studies but was shown in NMR to resemble asialo-GM₁. The production of multiple LOS forms and lack of GM₁ mimicry was not a result of phase variation in the genes tested of NCTC 11168 and was also observed in most of the human and chicken isolates of C. jejuni tested. Conclusion: The presence of differing amounts of LOS forms at 37 and 42°C, and the variety of forms observed in different strains, indicate that LOS form variation may play a role in an adaptive mechanism or a stress response of the bacterium during the colonization of different hosts.

Both Helicobacter pylori and Campylobacter jejuni are highly prevalent Gram-negative microaerophilic bacteria which are gastrointestinal pathogens of humans; H. pylori colonizes the gastroduodenal compartment and C. jejuni the intestinal mucosa. Although H. pylori causes chronic gastric infection leading to gastritis, peptic ulcers and eventually gastric cancer while C. jejuni causes acute infection inducing diarrhoeal disease, the endotoxin molecules of both bacterial species contrastingly contribute to their pathogenesis and the autoimmune sequelae each induces. Compared with enterobacterial endotoxin, that of H. pylori has significantly lower endotoxic and immuno-activities, the molecular basis for which is the underphosphorylation and underacylation of the lipid A component that interacts with immune receptors. This induction of low immunological responsiveness by endotoxin may aid the prolongation of H. pylori infection and therefore infection chronicity. On the other hand, this contrasts with acute infection-causing C. jejuni where overt inflammation contributes to pathology and diarrhoea production, and whose endotoxin is immunologically and endotoxically active. Futhermore, both H. pylori and C. jejuni exhibit molecular mimicry in the saccharide components of their endotoxins which can induce autoreactive antibodies; H. pylori expresses mimicry of Lewis and some ABO blood group antigens, C. jejuni mimicry of gangliosides. The former has been implicated in influencing the development of inflammation and gastric atrophy (a precursor of gastic cancer), the latter is central to the development of the neurological disorder Guillain-Barré syndrome. Both diseases raise important questions concerning infection-induced autoimmunity awaiting to be addressed.

Campylobacter jejuni is the leading bacterial cause of gastroenteritis worldwide. The present study was undertaken to determine the forms of polysacc

Campylobacter jejuni is a leading cause of gastroenteritis in humans. Campylobacter jejuni produces extracellular polysaccharides that have been char

Surfactant protein D (SP-D) is a collagenous glycoprotein, a collectin, which functions as a pathogen-associated molecular pattern (PAMP) recognition receptor in the innate immune response. Although originally identified in the lung as a component of surfactant, SP-D also occurs in the gastric mucosa at the luminal surface and within gastric pits of mucus-secreting cells. Infection with the gastroduodenal pathogen Helicobacter pylori up-regulates expression of SP-D in human patients with gastritis, and its influence on colonization has been demonstrated in a Helicobacter SP-D-deficient (SP-D(-/-)) mouse model. SP-D binds and agglutinates H. pylori cells in a lectin-specific manner, and has been shown to bind H. pylori lipopolysaccharide. Furthermore, evidence indicates that H. pylori varies LPS O-chain structure to evade SP-D binding which is speculated aids persistence of this chronic infection.

Surfactant protein D (SP-D) is a collagenous glycoprotein, a collectin, which functions as a pathogen-associated molecular pattern (PAMP) recognition receptor in the innate immune response. Although originally identified in the lung as a component of surfactant, SP-D also occurs in the gastric mucosa at the luminal surface and within gastric pits of mucus-secreting cells. Infection with the gastroduodenal pathogen Helicobacter pylori up-regulates expression of SP-D in human patients with gastritis, and its influence on colonization has been demonstrated in a Helicobacter SP-D-deficient (SP-D^{—/ —}) mouse model. SP-D binds and agglutinates H. pylori cells in a lectin-specific manner, and has been shown to bind H. pylori lipopolysaccharide. Furthermore, evidence indicates that H. pylori varies LPS O-chain structure to evade SP-D binding which is speculated aids persistence of this chronic infection.

Background.  Helicobacter pylori extrudes protein‐ and lipopolysaccharide‐enriched outer membrane vesicles from its cell surface which have been postulated to act to deliver virulence factors to the host. Lewis antigen expression by lipopolysaccharide of H. pylori cells has been implicated in a number of pathogenic roles. The aim of this study was to further characterize the expression of lipopolysaccharide on the surface of these outer membrane vesicles and, in particular, expression of Lewis antigens and their association with antibody production in the host.Materials and methods.  H. pylori strains were examined for outer membrane vesicle production using transmission electron microscopy and Lewis antigen expression probed using immunoelectron microscopy. Sera from patients were analyzed for cross‐reacting anti‐Lewis antibodies and, subsequently, absorbed using outer membrane vesicle preparations to remove the cross‐reacting antibodies.Results.  The formation of outer membrane vesicles by H. pylori was observed in both in vitro and in vivo samples. Furthermore, vesicles were produced following culture in either liquid or solid medium by all strains examined. Moreover, we observed the presence of Lewis epitopes on outer membrane vesicles using immunoelectron microscopy and immunoblotting. Circulating anti‐Lewis antibodies were found in the sera of gastric cancer patients but not in the sera of H. pylori‐negative control subjects. Absorption of patient sera with outer membrane vesicles decreased the levels of anti‐Lewis autoantibodies.Conclusions.  Our results demonstrate the ability of H. pylori to generate outer membrane vesicles bearing serologically recognizable Lewis antigens on lipopolysaccharide molecules which may contribute to the chronic immune stimulation of the host. The ability of these vesicles to absorb anti‐Lewis autoantibodies indicates that they may, in part, play a role in putative autoimmune aspects of H. pylori pathogenesis.