scholarly journals Immunization of Mice with Urease Vaccine Affords Protection against Helicobacter pylori Infection in the Absence of Antibodies and Is Mediated by MHC Class II–restricted Responses

1998 ◽  
Vol 188 (12) ◽  
pp. 2277-2288 ◽  
Author(s):  
Thomas H. Ermak ◽  
Paul J. Giannasca ◽  
Richard Nichols ◽  
Gwendolyn A. Myers ◽  
John Nedrud ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
B Cell ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Knockout Mice ◽  
Class Ii ◽  
Helicobacter Pylori Infection ◽  
Wild Type ◽  
H Pylori

We examined the roles of cell- and antibody-mediated immunity in urease vaccine–induced protection against Helicobacter pylori infection. Normal and knockout mice deficient in major histocompatibility complex (MHC) class I, MHC class II, or B cell responses were mucosally immunized with urease plus Escherichia coli heat-labile enterotoxin (LT), or parenterally immunized with urease plus aluminum hydroxide or a glycolipid adjuvant, challenged with H. pylori strain X47-2AL, and H. pylori organisms and leukocyte infiltration in the gastric mucosa quantified. In an adjuvant/route study in normal mice, there was a direct correlation between the level of protection and the density of T cells recruited to the gastric mucosa. In knockout studies, oral immunization with urease plus LT protected MHC class I knockout mice [β2-microglobulin (−/−)] but not MHC class II knockout mice [I-Ab (−/−)]. In B cell knockout mice [μMT (−/−)], vaccine-induced protection was equivalent to that observed in immunized wild-type (+/+) mice; no IgA+ cells were detected in the stomach, but levels of CD4+ cells equivalent to those in the wild-type strain (+/+) were seen. These studies indicate that protection of mice against H. pylori infection by immunization with the urease antigen is dependent on MHC class II–restricted, cell-mediated mechanisms, and antibody responses to urease are not required for protection.

scholarly journals Helicobacter pylori Infection in Immunized Mice Lacking Major Histocompatibility Complex Class I and Class II Functions

1999 ◽  
Vol 67 (1) ◽  
pp. 337-341 ◽  
Author(s):  
Jacques Pappo ◽  
Deirdre Torrey ◽  
Lillian Castriotta ◽  
Anneli Savinainen ◽  
Zita Kabok ◽  
...  
Keyword(s):  
Mhc Class I ◽  
Mhc Class Ii ◽  
Knockout Mice ◽  
Class Ii ◽  
Oral Immunization ◽  
Class I ◽  
Wild Type ◽  
Histocompatibility Complex ◽  
H Pylori

ABSTRACT The role of major histocompatibility complex (MHC) class I- and class II-restricted functions in Helicobacter pyloriinfection and immunity upon oral immunization was examined in vivo. Experimental challenge with H. pylori SS1 resulted in significantly greater (P ≤ 0.025) colonization of MHC class I and class II mutant mice than C57BL/6 wild-type mice. Oral immunization with H. pylori whole-cell lysates and cholera toxin adjuvant significantly reduced the magnitude of H. pylori infection in C57BL/6 wild-type (P = 0.0083) and MHC class I knockout mice (P = 0.0048), but it had no effect on the H. pylori infection level in MHC class II-deficient mice. Analysis of the anti-H. pyloriantibody levels in serum showed a dominant serum immunoglobulin G1 (IgG1) response in immunized C57BL/6 wild-type and MHC class I mutant mice but no detectable serum IgG response in MHC class II knockout mice. Populations of T-cell-receptor (TCR) αβ+CD4+ CD54+ cells localized to gastric tissue of immunized C57BL/6 wild-type and MHC class I knockout mice, but TCRαβ+ CD8+ cells predominated in the gastric tissue of immunized MHC class II-deficient mice. These observations show that CD4+ T cells engaged after mucosal immunization may be important for the generation of a protective anti-H. pylori immune response and that CD4+CD8− and CD4− CD8+ T cells regulate the extent of H. pylori infection in vivo.

scholarly journals Vaccine-Induced Protection against Helicobacter pylori in Mice Lacking Both Antibodies and Interleukin-4

2003 ◽  
Vol 71 (6) ◽  
pp. 3628-3633 ◽  
Author(s):  
Christine A. Garhart ◽  
John G. Nedrud ◽  
Frederick P. Heinzel ◽  
Norma E. Sigmund ◽  
Steven J. Czinn
Keyword(s):  
Helicobacter Pylori ◽  
B Cell ◽  
Knockout Mice ◽  
Cellular Responses ◽  
Interleukin 4 ◽  
Wild Type ◽  
Double Knockout ◽  
Th2 Response ◽  
H Pylori ◽  
Deficient Mice

ABSTRACT To test the hypothesis that a Th2 response to Helicobacter pylori is necessary for protection and to address the possibility that humoral and Th2 cellular responses may compensate for each other, we generated mice deficient in both interleukin-4 (IL-4) and antibodies. The immunized double-knockout mice were protected from H. pylori challenge, as were the parental strains and wild-type C57BL/6 mice. Neutralization of IL-4 in B-cell-deficient mice did not prevent protection. Immunized IL-5-deficient mice were also protected. Thus, IL-4 and IL-5 are not essential for protection.

scholarly journals Helicobacter pylori infection reduces the risk of gastroesophageal reflux disease

2021 ◽  
pp. 96-101
Author(s):  
R. I. Khlynova ◽  
O. M. Khromtsova ◽  
R. B. Berdnikov ◽  
I. B. Khlynov
Keyword(s):  
Helicobacter Pylori ◽  
Gastroesophageal Reflux Disease ◽  
Gastric Mucosa ◽  
Gastroesophageal Reflux ◽  
Observational Study ◽  
Reflux Disease ◽  
Helicobacter Pylori Infection ◽  
Cross Sectional ◽  
Biopsy Specimens ◽  
H Pylori

The aim is to study the effect of Helicobacter pylori infection on risk of developing gastroesophageal reflux disease. Materials and methods - cross-sectional observational study of 1007 patients with dyspepsia syndrome who underwent videoesophagogastroduodenoscopy with biopsy and histological examination of biopsy specimens of the gastric mucosa by OLGA-system. The age, gender, overweight, cigarette smoking, presence of Helicobacter pylori infection and gastritis stage were assessed. Results - the study showed a significant decrease in the incidence of gastroesophageal reflux disease in patients with positive H. Pylori status by 4% (RR 0,68; 95% CI, 0.49-0.94, p=0,041). The risk of developing gastroesophageal reflux disease significantly higher in overweight (RR 2,62; 95% CI 2,0-3,56; р<0,001) men (RR 1,76; 95% CI 1,33-2,32; р=0,0046) who smoked cigarettes (RR 3,23; 95% CI 2,45-4,24; р<0,001) and was not associated with the patient’s age and the stage of gastritis (р>0,05). Conclusion - a significant reduction in the frequency and risk of developing gastroesophageal reflux disease in patients with Helicobacter pylori infection is demonstrated.

scholarly journals The Exopolysaccharide of Lactobacillus fermentum UCO-979C Is Partially Involved in Its Immunomodulatory Effect and Its Ability to Improve the Resistance against Helicobacter pylori Infection

2020 ◽  
Vol 8 (4) ◽  
pp. 479
Author(s):  
Valeria Garcia-Castillo ◽  
Guillermo Marcial ◽  
Leonardo Albarracín ◽  
Mikado Tomokiyo ◽  
Patricia Clua ◽  
...  
Keyword(s):  
Immune Response ◽  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Helicobacter Pylori Infection ◽  
Beneficial Effects ◽  
Ifn Γ ◽  
H Pylori

Lactobacillus fermentum UCO-979C (Lf979C) beneficially modulates the cytokine response of gastric epithelial cells and macrophages after Helicobacter pylori infection in vitro. Nevertheless, no in vivo studies were performed with this strain to confirm its beneficial immunomodulatory effects. This work evaluated whether Lf979C improves protection against H. pylori infection in mice by modulating the innate immune response. In addition, we evaluated whether its exopolysaccharide (EPS) was involved in its beneficial effects. Lf979C significantly reduced TNF-α, IL-8, and MCP-1 and augmented IFN-γ and IL-10 in the gastric mucosa of H. pylori-infected mice. The differential cytokine profile induced by Lf979C in H. pylori-infected mice correlated with an improved reduction in the pathogen gastric colonization and protection against inflammatory damage. The purified EPS of Lf979C reduced IL-8 and enhanced IL-10 levels in the gastric mucosa of infected mice, while no effect was observed for IFN-γ. This work demonstrates for the first time the in vivo ability of Lf979C to increase resistance against H. pylori infection by modulating the gastric innate immune response. In addition, we advanced knowledge of the mechanisms involved in the beneficial effects of Lf979C by demonstrating that its EPS is partially responsible for its immunomodulatory effect.

scholarly journals Follow-up analysis and histopathological study of gastric mucosa in patients with Helicobacter pylori infection

2021 ◽  
Vol 49 (12) ◽  
pp. 030006052110553
Author(s):  
Guang Zhao ◽  
Zhishang Zhang ◽  
Baohui Li ◽  
Silin Huang ◽  
Wensi Li ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Intraepithelial Neoplasia ◽  
Mucosal Damage ◽  
Helicobacter Pylori Infection ◽  
Gastric Mucosal Damage ◽  
Histopathological Study ◽  
Significant Difference ◽  
H Pylori

Objective To investigate the histomorphological characteristics of the gastric mucosa and the prognosis in patients with Helicobacter pylori infection. Methods Progressive damage to the gastric mucosa was examined by immunohistochemistry in 2294 patients with H. pylori infection and follow-up information was analyzed. Results H. pylori initially colonized the mucus layer covered by the gastric mucosa epithelium, then selectively adhered to and destroyed the surface mucus cells causing intra-gastric and extra-gastric lesions. Gastric mucosal damage induced by H. pylori was divided into five stages according to the depth of H. pylori invasion and degree of lesion deterioration: mucilaginous, surface mucocellular, lamina propria lesion, mucosal atrophy, and intraepithelial neoplasia stages. Morphological follow-up analysis revealed no significant difference in 6-month curative effects between stage I and stage II, but significant differences were found between stages II and III, stages III and IV, and between stages IV and stage V, respectively. Conclusions This novel staging strategy may be a valuable tool for diagnosing and predicting the results of gastric mucosal damage induced by H. pylori infection.

Aberrant CpG Island Hypermethylation in Pediatric Gastric Mucosa in Association With Helicobacter pylori Infection

2011 ◽  
Vol 135 (6) ◽  
pp. 759-765
Author(s):  
So-Hyun Shin ◽  
Seog-Yun Park ◽  
Jae-Sung Ko ◽  
Nayoung Kim ◽  
Gyeong Hoon Kang
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Epithelial Cells ◽  
Cpg Island ◽  
Methylation Status ◽  
Helicobacter Pylori Infection ◽  
Gastric Epithelial Cells ◽  
Infected Adult ◽  
H Pylori ◽  
Methylight Assay

Abstract Context.—Helicobacter pylori infection is primarily acquired during childhood and persists throughout life in the absence of eradication with antibiotics. Helicobacter pylori infection induces methylation in the promoter CpG island loci in gastric epithelial cells. Thus, aberrant CpG island hypermethylation in gastric epithelial cells likely occurs early in life, although there are no existing data supporting this notion. Objectives.—To identify whether aberrant CpG island hypermethylation occurs in pediatric stomach mucosa in association with H pylori infection and to compare methylation profiles of samples from pediatric and adult stomach tissues. Design.—We analyzed pediatric (n  =  47) and adult (n  =  38) gastric mucosa samples for their methylation status in 12 promoter CpG island loci using the MethyLight assay and compared the number of methylated genes and the methylation levels in individual genes between H pylori–positive and H pylori–negative sample results and between pediatric and adult samples. Results.—The average number of methylated genes was significantly higher in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (3.4 versus 0.3, P &lt; .001) and in H pylori–infected adult samples than in H pylori–negative adult samples (7.6 versus 0.9, P &lt; .001). Seven genes showed significantly higher methylation levels in H pylori–infected pediatric samples than in H pylori–negative pediatric samples (all values were P &lt; .05). Conclusions.—These results indicate that CpG island hypermethylation occurs in pediatric gastric mucosa in association with H pylori infection and that the genes affected by H pylori–associated hypermethylation were similar in pediatric and adult samples.

Novel epitope based peptides for vaccine against SARS-CoV-2 virus: immunoinformatics with docking approach

2020 ◽  
Vol 8 (7) ◽  
pp. 2385 ◽  
Author(s):  
Jesvin Bency B. ◽  
Mary Helen P. A.
Keyword(s):  
B Cell ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Peptide Vaccine ◽  
Human Leukocyte ◽  
Respiratory Illness ◽  
Class Ii ◽  
Class I ◽  
T Cell Epitopes ◽  
B Cell Epitopes

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative viral strain for the contagious pandemic respiratory illness in humans which is a public health emergency of international concern. There is a desperate need for vaccines and antiviral strategies to combat the rapid spread of SARS-CoV-2 infection.Methods: The present study based on computational methods has identified novel conserved cytotoxic T-lymphocyte epitopes as well as linear and discontinuous B-cell epitopes on the SARS-CoV-2 spike (S) protein. The predicted MHC class I and class II binding peptides were further checked for their antigenic scores, allergenicity, toxicity, digesting enzymes and mutation.Results: A total of fourteen linear B-cell epitopes where GQSKRVDFC displayed the highest antigenicity-score and sixteen highly antigenic 100% conserved T-cell epitopes including the most potential vaccine candidates MHC class-I peptide KIADYNYKL and MHC class-II peptide VVFLHVTYV were identified. Furthermore, the potential peptide QGFSALEPL with high antigenicity score attached to larger number of human leukocyte antigen alleles. Docking analyses of the allele HLA-B*5201 predicted to be immunogenic to several of the selected epitopes revealed that the peptides engaged in strong binding with the HLA-B*5201 allele.Conclusions: Collectively, this research provides novel candidates for epitope-based peptide vaccine design against SARS-CoV-2 infection.

scholarly journals Tissue transglutaminase activity in human gastric mucosa according to Helicobacter pylori infection

2018 ◽  
Vol 243 (15-16) ◽  
pp. 1161-1164
Author(s):  
Maria Pina Dore ◽  
Giovanni Mario Pes ◽  
Alessandra Errigo ◽  
Alessandra Manca ◽  
Giuseppe Realdi
Keyword(s):  
Helicobacter Pylori ◽  
Animal Models ◽  
Gastric Mucosa ◽  
Natural History ◽  
Tissue Transglutaminase ◽  
Helicobacter Pylori Infection ◽  
Human Gastric Mucosa ◽  
Antral Mucosa ◽  
History Of ◽  
H Pylori

Tissue transglutaminase (t-TG) is a multifunctional protein involved in the healing of gastric erosions and ulcers in animal models. The aim of this study was to measure gastric t-TG activity in patients with dyspepsia according to Helicobacter pylori infection and cytotoxin-associated gene A (cagA) and vacuolating cytotoxin (vacA) subtype status. Patients undergoing upper endoscopy not taking any medications were enrolled. Tissue-TG activity was determined in homogenates of antral specimens using a radiometric assay and was expressed in pmol/mg. The cagA and vacA genotypes were determined by PCR amplification using gene-specific oligoprimers. Data from 46 patients were available (17 of them were positive for H. pylori). Antral t-TG activity was significantly increased in H. pylori positive patients compared to H. pylori negative patients (6437 ± 3691 vs. 3773 ± 1530 pmol/mg; P = 0.001) according to Mann–Whitney U test. Patients with H. pylori negative gastritis had higher t-TG activity than patients with normal gastric mucosa. The specimens infected with cagA positive strains (72%) displayed greater t-TG activity than cagA negative samples (7358 ± 4318 vs. 4895 ± 1062 pmol/mg; P = 0.237). Similarly, t-TG activity was higher in H. pylori vacA s1/m1 strains vs. vacA s1/m2 (7429 vs. 5045 pmol/mg; P = 0.744), and vacA s1/m1 vs. s2/m2 (7429 vs. 4489 pmol/mg; P = 0.651) but the results were not significant. No differences were found between histology, endoscopy features and t-TG activity. These results show that t-TG activity is significantly greater in gastritis associated with H. pylori infection, suggesting that this enzyme is induced by inflammation and may have an important role in the natural history of human gastritis. Impact statement Tissue transglutaminase (t-TG) is unique among TG enzymes because of its additional role in several physiological and pathological activities, including inflammation, fibrosis, and wound healing. The presence of t-TG has previously been described in the intestine of human and animal models, yet studies on t-TG activity in human gastric mucosa are missing. Helicobacter pylori infection is the major cause of gastritis and peptic ulcers. For the first time, our results show that t-TG activity was significantly higher in antral specimens of patients with chronic active gastritis associated with H. pylori infection compared to H. pylori negative chronic gastritis and normal antral mucosa. These findings suggest that t-TG has a role in the natural history of human gastritis, which requires further investigation but may be an avenue for new therapeutic options.

scholarly journals Helicobacter pylori Stores Nickel To Aid Its Host Colonization

2012 ◽  
Vol 81 (2) ◽  
pp. 580-584 ◽  
Author(s):  
Stéphane L. Benoit ◽  
Erica F. Miller ◽  
Robert J. Maier
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Mucosa ◽  
Physiological Role ◽  
Wild Type ◽  
Rank Tests ◽  
Content Type ◽  
Host Mouse ◽  
H Pylori ◽  
Very High

ABSTRACTThe transition metal nickel (Ni) is critical for the pathogenicity ofHelicobacter pylori. Indeed the element is a required component of two enzymes, hydrogenase and urease, that have been shown to be important forin vivocolonization of the host gastric mucosa. Urease accounts for up to 10% of the total cellularH. pyloriprotein content, and therefore the bacterial Ni demand is very high.H. pyloripossess two small and abundant histidine-rich, Ni-binding proteins, Hpn and Hpn-like, whose physiological role in the host have not been investigated. In this study, special husbandry conditions were used to control Ni levels in the host (mouse), including the use of Ni-free versus Ni-supplemented food. The efficacy of each diet was confirmed by measuring the Ni concentrations in sera of mice fed with either diet. Colonization levels (based on rank tests) of theΔhpn Δhpn-like double mutants isolated from the mice provided Ni-deficient chow were statistically lower than those for mice given Ni in their diet. In contrast,H. pyloriwild-type colonization levels were similar in both host groups (e.g., regardless of Ni levels). Our results indicate that the gastric pathogenH. pylorican utilize stored Ni via defined histidine-rich proteins to aid colonization of the host.

scholarly journals Colonization of C57BL/6J and BALB/c Wild-Type and Knockout Mice with Helicobacter pylori: Effect of Vaccination and Implications for Innate and Acquired Immunity

2003 ◽  
Vol 71 (2) ◽  
pp. 794-800 ◽  
Author(s):  
Klaus Panthel ◽  
Gerhard Faller ◽  
Rainer Haas
Keyword(s):  
Helicobacter Pylori ◽  
Knockout Mice ◽  
Tumor Necrosis Factor Receptor ◽  
Bacterial Pathogen ◽  
Interleukin 4 ◽  
Wild Type ◽  
Ulcer Disease ◽  
Knockout Mutants ◽  
Prophylactic Vaccination ◽  
H Pylori

ABSTRACT The gram-negative bacterial pathogen Helicobacter pylori is a major cause of peptic ulcer disease and a risk factor for gastric cancer in humans. Adapted H. pylori strains, such as strain SS1, are able to infect mice and are a useful model for gastric colonization and vaccination studies. In this study we used a streptomycin-resistant derivative of H. pylori SS1 to analyze the colonization behavior and the success of vaccination in wild-type (wt) and various knockout mice of the BALB/c and C57BL/6J genetic backgrounds. We here report that BALB/c interleukin-4 knockout (IL-4−/−) mice are weakly overcolonized compared to the wt strain but that the IL-12−/− knockout results in a strong overcolonization (500%). Unexpectedly, in the C57BL/6J background the same knockouts behaved in diametrically opposed manners. The IL-4−/− mutation caused a 50% reduction and the IL-12−/− knockout caused a 95% reduction compared to the wt colonization rate. For C57BL/6J mice we further analyzed the IL-18−/− and Toll-like receptor 2 knockout mutations, which showed reductions to 66 and 57%, respectively, whereas mice with the IL-10−/− phenotype were hardly infected at all (5%). In contrast, the tumor necrosis factor receptor knockout (p55−/− and p55/75−/−) mice showed an overcolonization compared to the C57BL/6J wt strain. With exception of the low-level infected C57BL/6J IL-10−/− and IL-12−/− knockout mice, all knockout mutants were accessible to a prophylactic vaccination and their vaccination behavior was comparable to that of the wt strains.

Sign in / Sign up

Export Citation Format

Share Document