The role of toll-like receptors in immune tolerance induced by Helicobacter pylori infection

Helicobacter pylori (H. pylori) is a gram-negative, microaerobic bacterium that colonizes the gastric mucosa in about half of the world's population. H. pylori infection can lead to various diseases. Chronic infection by H. pylori exposes the gastric mucosa to bacterial components such as lipopolysaccharide (LPS), outer membrane vesicles (OMVs), and several toxic proteins. Infected with H. pylori activates the release of pro-inflammatory factors and triggers inflammatory responses that damage the gastric mucosa. As the only microorganism that permanently colonizes the human stomach, H. pylori can suppress host immunity to achieve long-term colonization. Toll-like receptors (TLRs) play a crucial role in T-cell activation, promoting innate immune responses and immune tolerance during H. pylori infection. Among the 10 TLRs found in humans, TLR2, TLR4, TLR5, and TLR9 have been thoroughly investigated in relation to H. pylori-linked immune regulation. In the present review, we provide a comprehensive analysis of the various mechanisms employed by different TLRs in the induction of immune tolerance upon H. pylori infection, which will contribute to the research of pathogenic mechanism of H. pylori.     

Role of Immune Serum in the Killing of Helicobacter pylori by Macrophages

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.     

The Interaction Between Helicobacter pylori and Atopy: Does Inverse Association Really Exist?

Aim: To date, cross‐sectional and case–control studies suggest an inverse association between Helicobacter pylori infection and atopic diseases, whereas the immunologic basis has not been studied yet. In this study we investigated T helper (Th) cell function in H. pylori‐infected children and compared cytokine responses in atopic and non‐atopic groups. Methods: The study groups was recruited from a cohort of 327 healthy children evaluated and followed‐up for 6 years to assess the natural history of H. pylori infection. Seventy‐four of 136 healthy children who underwent ¹³C urea breath test were eligible and accepted to participate. All participants were evaluated by a questionnaire, and skin‐prick testing. According to the results, children were divided into four groups with respect to the presence or absence of H. pylori and atopy. Peripheral blood mononuclear cells isolated from 34 of 74 children were cultured with H. pylori, Der p 1, and phytohemagglutinin (PHA). Interferon‐gamma (IFN‐γ), interleukin (IL)‐4 and IL‐10, transforming growth factor‐beta (TGF‐β) levels were measured in supernatants. Results: The frequency of atopy was lower in H. pylori‐infected group (31.9% vs. 48.1, p = .22), while atopic symptoms were similar between infected and non‐infected children. While PHA and H. pylori induced IFN‐γ levels were significantly higher in H. pylori‐infected children, concomitant presence of both atopy and H. pylori decreased the level of PHA and H. pylori induced IFN‐γ production. PHA and Der p 1‐induced IL‐4 levels were higher in atopic children, and IL‐4 production was suppressed when they were concomitantly infected with H. pylori. The production of TGF‐β was found to be suppressed in atopic children irrespective of the presence of H. pylori infection. Conclusion: The results of the current study demonstrated a counteractive Th1 and Th2 cytokine interaction between H. pylori infection and atopy. However, this counteractive immunologic balance did not protect against atopy.     

A coordinated cytotoxic effect of IFN-gamma and cross-reactive antibodies in the pathogenesis of Helicobacter pylori gastritis

Background. Helicobacter pylori (H. pylori) infection is associated with chronic infiltration into the stomach by T cells and plasma cells producing IFN‐γ and antibodies of various specificities, respectively. It is unknown whether these lymphocyte‐products may play coordinated roles in the gastric pathology of this infection. Aims. To know how IFN‐γ may relate to anti‐H. pylori antibodies in their roles in pathogenesis, we determined the isotype subclass of those antibodies as well as their cross‐reactivity and cytotoxicity to gastric epithelium. Methods and Results. We infected BALB/c mice with H. pylori (SS1, Sydney Strain 1) and generated monoclonal antibodies, which were comprised of 240 independent clones secreting immunoglobulin and included 80 clones reactive to SS1. Ninety percent of the SS1‐reactive clones had IgG2a isotype. Two clones, 2B10 and 1A9, were cross reactive to cell surface antigens in H. pylori and to antigens of 28 KDa and 42 KDa, respectively, which were present on the cell surface of and shared by both mouse and human gastric epithelial cells. The antigens recognized by these monoclonal antibodies localized a distinctive area in the gastric glands. In the presence of complement, 2B10 showed cytotoxicity to gastric epithelial cells. The effect was dose dependant and augmented by IFN‐γ. Finally, administration of 2B10 to mice with SS1 infection aggravated gastritis by increasing cellular infiltration. Conclusion. IFN‐γ by gastric T cells may participate in pathogenesis of the H. pylori infected stomach by directing an isotype‐switch of anti‐H. pylori antibodies to complement‐binding subclass and by augmenting cytotoxic activity of a certain autoantibody. This may explain a host‐dependent diversity in gastric pathology of the patients with H. pylori infection.     

The impact of autophagic processes on the intracellular fate of Helicobacter pylori

Helicobacter pylori is a Gram-negative pathogen that colonizes the gastric epithelium of 50–60% of the world’s population. Approximately one-fifth of the infected individuals manifest severe diseases such as peptic ulcers or gastric cancer. H. pylori infection has proven difficult to cure despite intensive antibiotic treatment. One possible reason for the relatively high resistance to antimicrobial therapy is the ability of H. pylori to reside inside host cells. Although considered by most as an extracellular pathogen, H. pylori can invade both gastric epithelial cells and immunocytes to some extent. The intracellular survival of H. pylori has been implicated in its ability to persist in the stomach, evade host immune responses and resist eradication by membrane-impermeable antibiotics. Interestingly, recent evidence suggests that macroautophagy, a cellular self-degradation process characterized by the formation of double-membraned autophagosomes, plays an important role in determining the intracellular fate of H. pylori. Detailed understanding of the interaction between H. pylori and host cell autophagic processes is anticipated to provide novel insights into the molecular mechanisms of macroautophagy and H. pylori pathogenesis, opening new avenues for the therapeutic intervention of autophagy-related and H. pylori-related disorders.     

Helicobacter pylori infection up-regulates gland mucous cell-type mucins in gastric pyloric mucosa

Background. Two types of mucous cell are present in gastric mucosa: surface mucous cells (SMCs) and gland mucous cells (GMCs), which consist of cardiac gland cells, mucous neck cells, and pyloric gland cells. We have previously reported that the patterns of glycosylation of SMC mucins are reversibly altered by Helicobacter pylori infection. In this study, we evaluated the effects of H. pylori infection on the expression of GMC mucins in pyloric gland cells. Methods. Gastric biopsy specimens from the antrums of 30 H. pylori‐infected patients before and after eradication of H. pylori and 10 normal uninfected volunteers were examined by immunostaining for MUC6 (a core protein of GMC mucins), α1,4‐N‐acetyl‐glucosaminyl transferase (α4GnT) (the glycosyltransferase which forms GlcNAcα1‐4Galβ‐R), and GlcNAcα1‐4Galβ‐R (a GMC mucin‐specific glycan). Results. MUC6, α4GnT, and HIK1083‐reactive glycan were expressed in the cytoplasm, supranuclear region, and secretory granules in pyloric gland cells, respectively. The immunoreactivity of MUC6 and α4GnT, but not of GlcNAcα1‐4Galβ‐R, in the pyloric gland increased in H. pylori‐associated gastritis, and after the eradication of H. pylori, the increased expression of MUC6 and α4GnT in the gastric mucosa of H. pylori‐infected patients decreased to almost normal levels. This up‐regulation was correlated with the degree of inflammation. Conclusions. In addition to the synthesis of GMC mucins increasing reversibly, their metabolism or release may also increase reversibly in H. pylori‐associated gastritis. The up‐regulation of the expression of gastric GMC mucins may be involved in defense against H. pylori infection in the gastric surface mucous gel layer and on the gastric mucosa.     

Effects of selective cyclooxygenase-2 inhibitor and non-selective NSAIDs on Helicobacter pylori-induced gastritis in Mongolian gerbils

Background. It is still a point of controversy whether Helicobacter pylori‐infected patients are more likely to develop mucosal damage while taking NSADIs. Selective cyclooxygenase (COX‐2) inhibitors may be associated with less severe gastric mucosal damage than conventional NSAIDs, but this association is undefined in H. pylori‐induced gastritis. The aim of this study was to evaluate the effects of selective COX‐2 and nonselective NSAIDs on H. pylori‐induced gastritis. Methods. After intragastric administration of indomethacin, NS‐398 or vehicle alone, once daily for 5 days in H. pylori‐infected and uninfected Mongolian gerbils, we evaluated gastric mucosal damage, inflammatory cell infiltration and prostaglandin E₂ (PGE₂) concentration. We investigated whether H. pylori infection induced the COX‐2 expression. Results. In H. pylori‐uninfected groups, the indomethacin‐treated group showed the highest mucosal damage score and the lowest PGE₂ concentration. There was no difference in mucosal damage scores and PGE₂ concentration between NS‐398 and vehicle‐alone treated group. In H. pylori‐infected groups, there was no difference in mucosal damage scores, irrespective of the type of drugs administered. The indomethacin‐treated group showed the lowest PGE₂ concentration, similar to that of the NS‐398 and vehicle‐alone treated groups, both without H. pylori infection. Gastric neutrophil and monocyte infiltration scores were higher in H. pylori‐infected groups than in uninfected groups. However, there was no difference in these scores according to the type of drugs administered, within H. pylori‐infected or uninfected groups. COX‐2 protein expression was observed in H. pylori‐infected Mongolian gerbils but not in uninfected ones. Conclusions. Our animal study showed that H. pylori infection induced COX‐2 expression and increased prostaglandin concentration. Administration of NSAIDs decreased the prostaglandin concentration, but did not increase mucosal damage in H. pylori‐induced gastritis. Selective COX‐2 inhibitors, instead of conventional NSIADs, had no beneficial effect on preventing mucosal damage in H. pylori‐induced gastritis.     

Helicobacter pylori Induces Inflammation in Mouse Urinary Bladder and Pelvis

Helicobacter pylori was transurethrally inoculated into the mouse urinary tract. The organism established infection and induced inflammation in the urinary bladder and pelvis. During the infection, urinary pH was elevated, probably due to the production of NH3 by bacterial urease. H. pylori was recovered from the urinary bladder, kidney and urine of the infected mice. Histopathologically, severe neutrophil infiltration was observed in the mucosal layer of both organs. H. pylori was detected on the surface of the epithelial cells. These results indicate that low pH and bacterial flora were not essential factors in establishing the mucosal infection with H. pylori. This experimental system is useful to investigate the pathogenicity of H. pylori in mucosal organs.     

Compromised autophagy by MIR30Bbenefits the intracellular survival of Helicobacter pylori

Helicobacter pylori evade immune responses and achieve persistent colonization in the stomach. However, the mechanism by which H. pylori infections persist is not clear. In this study, we showed that MIR30B is upregulated during H. pylori infection of an AGS cell line and human gastric tissues. Upregulation of MIR30B benefited bacterial replication by compromising the process of autophagy during the H. pylori infection. As a potential mechanistic explanation for this observation, we demonstrate that MIR30B directly targets ATG12 and BECN1, which are important proteins involved in autophagy. These results suggest that compromise of autophagy by MIR30B allows intracellular H. pylori to evade autophagic clearance, thereby contributing to the persistence of H. pylori infections.     

Increased gastric osteopontin expression by Helicobacter pylori Infection can correlate with more severe gastric inflammation and intestinal metaplasia

Background: Osteopontin (OPN) is involved in the gastric cancer progression. The study validated whether OPN expressions correlate with Helicobacter pylori‐related chronic gastric inflammation and the precancerous change as intestinal metaplasia (IM). Methods: This study included 105 H. pylori‐infected patients (63 without and 42 with IM) and 29 H. pylori‐negative controls. In each subject, the gastric OPN expression intensity was evaluated by immunohistochemistry, and graded from 0 to 4 for the epithelium, lamina propria, and areas with IM, respectively. For the H. pylori‐infected subjects, the gastric inflammation was assessed by the Updated Sydney System. Forty‐nine patients received follow‐up endoscopy to assess OPN change on gastric mucosa after H. pylori eradication. The in vitro cell‐H. pylori coculture were performed to test the cell origin of OPN. Results: The H. pylori‐infected patients had higher gastric OPN expression than the noninfected controls (p < .001). For the H. pylori‐infected patients, an increased OPN expression correlated with more severe chronic gastric inflammation (p < .001) and the presence of IM (OR: 2.6, 95% CI: 1.15–5.94, p = .02). Within the same gastric bits, lamina propria expressed OPN stronger than epithelium (p < .001), suggesting OPN predominantly originates from inflammatory cells. The in vitro assay confirmed H. pylori stimulate OPN expression in the monocytes, but not in the gastric epithelial cells. After H. pylori eradication, the gastric OPN expression could be decreased only in areas without IM (p < .05). Conclusions: Increased gastric OPN expression by H. pylori infection can correlate with a more severe gastric inflammation and the presence of IM.     

Lectin histochemistry of the gastric mucosa in normal and Helicobacter pylori infected guinea-pigs

Helicobacter pylori attaches via lectins, carbohydrate binding proteins, to the carbohydrate residues of gastric mucins. Guinea-pigs are a suitable model for a H. pylori infection and thus the carbohydrate composition of normal and H. pylori infected gastric mucosa was investigated by lectin histochemistry. The stomach of all infected animals showed signs of an active chronic gastritis in their mucosa, whereas no inflammation was present in the control animals. The corpus–fundus regions of the controls showed heterogeneous WGA, SNA-I, UEA-I and HPA binding in almost all parts of the gastric glands. While these lectins labelled the superficial mucous cells and chief cells heterogeneously, the staining of the parietal cells was limited to WGA and PHA-L. Mucous neck cells reacted heterogeneously with UEA-I, HPA, WGA and PHA-L. In the antrum, the superficial mucous cells and glands were stained by WGA, UEA-I, HPA, SNA-I or PHA-L. WGA, UEA-I, SNA-I and HPA labelled the surface lining cells strongly. The mucoid glands reacted heterogeneously with WGA, UEA-I, HPA, SNA-I and PHA-L. In both regions, the H. pylori infected animals showed similar lectin binding pattern as the controls. No significant differences in the lectin binding pattern and thus in the carbohydrate composition between normal and H. pylori infected mucosa could be detected, hence H. pylori does not induce any changes in the glycosylation of the mucosa of the guinea-pig. This unaltered glycosylation is of particular relevance for the sialic acid binding lectin SNA-I as H. pylori uses sialic acid binding adhesin for its attachment to the mucosa. As sialic acid binding sites are already expressed in the normal mucosa H. pylori can immediately attach via its sialic acid binding adhesin to the mucosa making the guinea-pig particularly useful as a model organism.This work is dedicated to Professor B. Tillmann on the occasion of his 65th birthday     

p16Ink4a is overexpressed in H. pylori-associated gastritis and is correlated with increased epithelial apoptosis

Background. Cell cycle regulatory proteins may be critical targets during carcinogenesis. We have previously shown that chronic H. pylori infection is associated with decreased expression of the cyclin dependent kinase inhibitor (CDI) p27^kip1. Loss of p27^kip1 and p16^Ink4a (p16) expression, another CDI, has been reported during the progression of gastric tubular adenomas to advanced gastric cancer. The aim of the current study was to examine whether H. pylori infection also affects the expression of p16 in the gastric mucosa of H. pylori‐infected patients. Methods. p16 expression was evaluated in gastric antral biopsies by immunohistochemistry in 50 patients with nonulcer dyspepsia (n = 18 uninfected, n = 32 H. pylori infected, 24 by cagA⁺ strains). Adjacent sections were stained for proliferating epithelial cells (by Ki67) and for apoptotic cells (by TUNEL assay). Results. Both in H. pylori infected and uninfected patients the expression of p16 was higher in the neck and base of the gland than in the foveolar region. Epithelial staining for p16 was increased with H. pylori infection (31.3% vs. 11.1% in the foveolar region, 68.8% vs. 27.8% in the neck and 75% vs. 50% in the glandular base). There was no correlation between the expression of 16 and proliferation but there was a significant positive correlation between apoptosis and 16 immunostaining. Conclusions. The tumor suppressor gene 16 is over expressed in gastric epithelial cells of H. pylori infected patients and this is associated with an increase in apoptosis. These findings suggest a possible role for this cell cycle regulator in the increase in gastric cell turnover that is associated with H. pylori infection.     

The human gastric pathogen Helicobacter pylori has a gene encoding an enzyme first classified as a mucinase in Vibrio cholerae

The human bacterial pathogen Helicobacter pylori has been suggested to be the causative agent of the most common chronic infection of man. Since its first isolation in 1982, H. pylori has been associated with gastric and duodenal ulcer disease, and more recently, gastric cancer. The proteolytic digestion of gastric mucus by this microorganism has been suggested as an important mechanism by which its pathogenicity is at least partly exerted. Here we report the detection of protease activity in H. pylori total-cell and supernatant extracts. On the basis that zinc metalloproteases are common microbial pathogenicity factors, we identified a single protein in H. pylori protein extracts with antibodies to the Pseudomonas aeruginosa elastase (a secreted zinc metallo-protease). This same protein was identified by pooled serum from patients infected with H. pylori. We used the functional and immunological relationship between the P. aeruginosa elastase and the Vibrio cholerae haemagglutinin/protease (HAP) to clone the H. pylori hap gene, which was over 99% similar to the V. cholerae hap gene in the coding region. A 4 kb DNA fragment containing the entire cloned gene was highly unstable in Escherichia coli and Bacillus subtilis cloning vectors. We also demonstrated that a hap-like gene sequence is present in ail nine Helicobacter species so far discovered. The V. cholerae HAP was first classified on the basis of its mucinase activity.     

Superoxide dismutase from Helicobacter pylori suppresses the production of pro‐inflammatory cytokines during in vivo infection

Background

Helicobacter pylori has undergone considerable adaptation to allow chronic persistence within the gastric environment. While H. pylori‐associated diseases are driven by an excessive inflammation, severe gastritis is detrimental to colonization by this pathogen. Hence, H. pylori has developed strategies to minimize the severity of gastritis it triggers in its host. Superoxide dismutase (SOD) is well known for its role in protecting against oxidative attack; less recognized is its ability to inhibit immunity, shown for SOD from mammalian sources and those of some bacterial species. This study examined whether H. pylori SOD (HpSOD) has the ability to inhibit the host immune response to these bacteria.

Materials and Methods

The ability of recombinant HpSOD to modify the response to LPS was measured using mouse macrophages. A monoclonal antibody against HpSOD was generated and injected into H. pylori‐infected mice.

Results

Addition of HpSOD to cultures of mouse macrophages significantly inhibited the pro‐inflammatory cytokine response to LPS stimulation. A monoclonal antibody was generated that was specific for SOD from H. pylori. When injected into mice infected with H. pylori for 3 months, this antibody was readily detected in both sera and gastric tissues 5 days later. While treatment with anti‐HpSOD had no effect on H. pylori colonization at this time point, it significantly increased the levels of a range of pro‐inflammatory cytokines in the gastric tissues. This did not occur with antibodies against other antioxidant enzymes.

Conclusions

SOD from H. pylori can inhibit the production of pro‐inflammatory cytokine during in vivo infection.     

Up-regulation of inducible nitric oxide synthase and nitric oxide in Helicobacter pylori-infected human gastric epithelial cells: possible role of interferon-gamma in polarized nitric oxide secretion

Background. Nitric oxide (NO) generated by nitric oxide synthase (NOS) is known to be an important modulator of the mucosal inflammatory response. In this study, we questioned whether Helicobacter pylori infection could up‐regulate the epithelial cell inducible NOS (iNOS) gene expression and whether NO production could show polarity that can be regulated by immune mediators. Materials and Methods. Human gastric epithelial cell lines were infected with H. pylori, and the iNOS mRNA expression was assessed by quantitative RT‐PCR. NO production was assayed by determining nitrite/nitrate levels in culture supernatants. To determine the polarity of NO secretion by the H. pylori‐infected epithelial cells, Caco‐2 cells were cultured as polarized monolayers in transwell chambers, and NO production was measured. Results. iNOS mRNA levels were significantly up‐regulated in the cells infected with H. pylori, and expression of iNOS protein was confirmed by Western blot analysis. Increased NO production in the gastric epithelial cells was seen as early as 18 hours postinfection, and reached maximal levels by 24 hours postinfection. The specific MAP kinase inhibitors decreased H. pylori‐induced iNOS and NO up‐regulation. After H. pylori infection of polarized epithelial cells, NO was released predominantly into the apical compartment, and IL‐8 was released predominantly into basolateral compartment. The addition of IFN‐γ to H. pylori‐infected polarized epithelial cells showed a synergistically higher apical and basolateral NO release. Conclusion. These results suggest that apical NO production mediated by MAP kinase in H. pylori‐infected gastric epithelial cells may influence the bacteria and basolateral production of NO and IL‐8 may play a role in the tissue inflammation.     

Crohn disease ATG16L1 polymorphism increases susceptibility to infection with Helicobacter pylori in humans

Autophagy plays key roles both in host defense against bacterial infection and in tumor biology. Helicobacter pylori (H. pylori) infection causes chronic gastritis and is the single most important risk factor for the development of gastric cancer in humans. Its vacuolating cytotoxin (VacA) promotes gastric colonization and is associated with more severe disease. Acute exposure to VacA initially triggers host autophagy to mitigate the effects of the toxin in epithelial cells. Recently, we demonstrated that chronic exposure to VacA leads to the formation of defective autophagosomes that lack CTSD/cathepsin D and have reduced catalytic activity. Disrupted autophagy results in accumulation of reactive oxygen species and SQSTM1/p62 both in vitro and in vivo in biopsy samples from patients infected with VacA⁺ but not VacA^- strains. We also determined that the Crohn disease susceptibility polymorphism in the essential autophagy gene ATG16L1 increases susceptibility to H. pylori infection. Furthermore, peripheral blood monocytes from individuals with the ATG16L1 risk variant show impaired autophagic responses to VacA exposure. This is the first study to identify both a host autophagy susceptibility gene for H. pylori infection and to define the mechanism by which the autophagy pathway is affected following H. pylori infection. Collectively, these findings highlight the synergistic effects of host and bacterial autophagy factors on H. pylori pathogenesis and the potential for subsequent cancer susceptibility.     

Protein changes in gastric epithelial cells RGM-1 in response to Helicobacter pylori infection

Helicobacter pylori-induced inflammation significantly increases the risk of gastric cancer. To investigate the role of H. pylori infection in gastric epithelial cell carcinogenesis, flow cytometry was used to analyze the apoptosis of gastric epithelial cells infected by H. pylori. Next, LTQ MS mass spectrometry (MS) was applied to identify protein changes in gastric epithelial cells infected with H. pylori, and then bioinformatics was adopted to analyze the cellular localization and biological function of differential proteins. LTQ MS/MS successfully identified identified 22 differential proteins successfully, including 20 host-cell proteins and two H. pylori bacterial proteins. Also, human proteins were located in all areas of cells and involved in various cell biological functions. The oncogene proteins p53, p16, and C-erbB-2 proteins in H. pylori-infected RGM-1 cells were remarkably increased from the analysis by Western blot analysis. H. pylori infection of gastric epithelial cells leads to changes in various protein components in the cell, and enhances the expression of oncogene proteins, thereby increasing the possibility of possibility of carcinogenesis of H. pylori infection.     

Are individuals with lower neutrophil oxidative burst activity more prone to Helicobacter pylori infection?

Helicobacter pylori infection has been reported to cause enhanced reactive oxygen species in the gastric mucosa. We examined the relationship between H. pylori infection and neutrophil function of peripheral blood. The subjects were 904 volunteers who participated in the Iwaki Health Promotion Project in 2005. 158 subjects who were infected with H. pylori in 2005 also participated in this project in 2006 and were categorized into two groups: the eradication group, in which H. pylori was successfully eradicated during the 12 month period, and the non‐eradication group, in which eradication was unsuccessful or the subjects did not receive eradication therapy. The laboratory assays performed were: a titre of H. pylori antibody; neutrophil counts; and oxidative burst activity (OBA) of neutrophils. Logistic regression analysis was executed, with H. pylori infection as the dependent variable and other items as the independent variables. OBA showed an inverse association with H. pylori infection in 2005. Additionally, when comparing the eradication and non‐eradication groups, the change rates of OBA between 2005 and 2006 did not show any significant difference. It was concluded that H. pylori infection does not lower OBA, but those individuals in whom OBA was lower were more prone to H. pylori infection. Copyright © 2008 John Wiley & Sons, Ltd.