scholarly journals Possible Correlates of Long-Term Protection against Helicobacter pylori following Systemic or Combinations of Mucosal and Systemic Immunizations

2007 ◽  
Vol 75 (7) ◽  
pp. 3462-3469 ◽  
Author(s):  
Jennifer M. Taylor ◽  
Melanie E. Ziman ◽  
Julie Fong ◽  
Jay V. Solnick ◽  
Michael Vajdy
Keyword(s):  
Helicobacter Pylori ◽  
Protective Immunity ◽  
Interleukin 12 ◽  
Effective Vaccine ◽  
Correlates Of Protection ◽  
Oral Group ◽  
Efficient Route ◽  
H Pylori

ABSTRACT The ability to induce long-term immunity to Helicobacter pylori is necessary for an effective vaccine. This study was designed to establish the most efficient route(s) (systemic, mucosal, or a combination) of immunization for induction of long-term immunity and to define correlates of protection. Mice were immunized orally alone (oral group), intramuscularly (i.m.) alone (i.m. group), orally followed by i.m. (oral/i.m. group), or i.m. followed by orally (i.m./oral group). Long-term protective immunity to oral H. pylori challenge was observed 3 months after immunization through the i.m. or oral/i.m. route. Protection correlated with an increase in H. pylori-specific interleukin-12 and both immunoglobulin G1 (IgG1) and IgG2a serum titers following challenge. Mice that were not protected (oral or i.m./oral) had increased levels of IgA in both sera and Peyer's patches. This study demonstrates the ability to induce long-term immunity against H. pylori, provides correlates of protection, and illustrates the crucial role of the immunization route(s).

scholarly journals The role of Helicobacter pylori in metabolic and cardiovascular diseases

2021 ◽  
pp. 86-95
Author(s):  
T. E. Kugler ◽  
G. G. Taradin ◽  
R. Pellicano
Keyword(s):  
Helicobacter Pylori ◽  
Cardiovascular Diseases ◽  
Diagnostic Methods ◽  
Alcoholic Fatty Liver ◽  
High Prevalence ◽  
High Incidence ◽  
H Pylori ◽  
Alcoholic Fatty Liver Disease

Helicobacter pylori (H. pylori) infection is one of the most common in the world. More than 50% of the world’s population is infected and infection rates are especially high in countries with poor socio-economic conditions. H. pylori causes gastroduodenal and extra-gastroduodenal diseases including such metabolic disorders as obesity, diabetes mellitus and non-alcoholic fatty liver disease. Recent epidemiological and clinical studies showed that the long-term persistence of H. pylori infection is associated with the development and progression of atherosclerosis and consequently cardiovascular diseases. However, the correlation between these conditions is ambiguous and there is not enough evidence to confirm it. The lack of consensus might be related to differences in diagnostic methods used for H. pylori and the variety of its genotypes. Considering high prevalence of H. pylori infection as well as high incidence of metabolic and cardiovascular diseases, a verified correlation between these can be of great epidemiological, prophylactic and clinical significance.

scholarly journals Helicobacter pylori: From Bench to Bedside

1997 ◽  
Vol 11 (7) ◽  
pp. 589-596 ◽  
Author(s):  
N Chiba ◽  
A Matisko ◽  
P Sinclair ◽  
ABR Thomson
Keyword(s):  
Helicobacter Pylori ◽  
Paradigm Shift ◽  
Eradication Rate ◽  
Good Clinical Practice ◽  
Effective Vaccine ◽  
Ulcer Disease ◽  
Exponential Increase ◽  
Major Interest ◽  
H Pylori

With the exponential increase in research in the field ofHelicobacter pyloria paradigm shift has occurred. It is now recognized thatH pyloriis a chronic infection of the stomach causing inflammation. Some patients remain asymptomatic, while others may develop dyspepsia, duodenal or gastric ulcer, gastric cancer or a mucosa-associated lymphoid tissue lymphoma. However, the role ofH pyloriin contributing to nonulcer dyspepsia or nonsteroidal anti-inflammatory drug gastropathy remains controversial. An effective vaccine againstH pyloriis years away. Major interest has focused on the questions "who should be investigated and therefore treated" and "what is the latest gold standard for eradication ofH pylori"? In Europe, guidelines have been developed to help the practitioner answer these important questions. Canadian guidelines will soon be available. For persons with known peptic ulcer disease there should be unequivocal acceptance that the good clinical practice of eradicatingH pyloriwill result in substantial savings in health care expenses. The original 'classical triple therapy' (bismuth, metronidazole and tetracycline [BMT]) has now been surpassed by the combination of a proton pump inhibitor (PPI) plus two antibiotics (metronidazole plus clarithromycin; amoxicillin plus clarithromycin; or amoxicillin plus metronidazole), each given twice a day for one week. In Canada, the regimen of omeprazole plus one antibiotic (amoxicillin or clarithromycin) was approved recently but gives an eradication rate that is lower than the current target of 90%. According to the European (Mäastricht) recommendations, if a single treatment attempt with PPI plus two antibiotics fails, PPI plus BMT is recommended.

scholarly journals Whole-Genome Sequencing and Comparative Genomics of Three Helicobacter pylori Strains Isolated from the Stomach of a Patient with Adenocarcinoma

Pathogens ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 331
Author(s):  
Montserrat Palau ◽  
Núria Piqué ◽  
M. José Ramírez-Lázaro ◽  
Sergio Lario ◽  
Xavier Calvet ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Virulence Factors ◽  
Outer Membrane Proteins ◽  
Whole Genome ◽  
Flagellar Biosynthesis ◽  
H Pylori ◽  
Restriction Modification

Helicobacter pylori is a common pathogen associated with several severe digestive diseases. Although multiple virulence factors have been described, it is still unclear the role of virulence factors on H. pylori pathogenesis and disease progression. Whole genome sequencing could help to find genetic markers of virulence strains. In this work, we analyzed three complete genomes from isolates obtained at the same point in time from a stomach of a patient with adenocarcinoma, using multiple available bioinformatics tools. The genome analysis of the strains B508A-S1, B508A-T2A and B508A-T4 revealed that they were cagA, babA and sabB/hopO negative. The differences among the three genomes were mainly related to outer membrane proteins, methylases, restriction modification systems and flagellar biosynthesis proteins. The strain B508A-T2A was the only one presenting the genotype vacA s1, and had the most distinct genome as it exhibited fewer shared genes, higher number of unique genes, and more polymorphisms were found in this genome. With all the accumulated information, no significant differences were found among the isolates regarding virulence and origin of the isolates. Nevertheless, some B508A-T2A genome characteristics could be linked to the pathogenicity of H. pylori.

scholarly journals Systems Modeling of the Role of Interleukin-21 in the Maintenance of Effector CD4+ T Cell Responses during Chronic Helicobacter pylori Infection

mBio ◽  
2014 ◽  
Vol 5 (4) ◽  
Author(s):  
Adria Carbo ◽  
Danyvid Olivares-Villagómez ◽  
Raquel Hontecillas ◽  
Josep Bassaganya-Riera ◽  
Rupesh Chaturvedi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
T Cell ◽  
Wild Type ◽  
Content Type ◽  
Interleukin 21 ◽  
H Pylori ◽  
Deficient Mice

ABSTRACTThe development of gastritis duringHelicobacter pyloriinfection is dependent on an activated adaptive immune response orchestrated by T helper (Th) cells. However, the relative contributions of the Th1 and Th17 subsets to gastritis and control of infection are still under investigation. To investigate the role of interleukin-21 (IL-21) in the gastric mucosa duringH. pyloriinfection, we combined mathematical modeling of CD4+T cell differentiation within vivomechanistic studies. We infected IL-21-deficient and wild-type mice withH. pyloristrain SS1 and assessed colonization, gastric inflammation, cellular infiltration, and cytokine profiles. ChronicallyH. pylori-infected IL-21-deficient mice had higherH. pyloricolonization, significantly less gastritis, and reduced expression of proinflammatory cytokines and chemokines compared to these parameters in infected wild-type littermates. Thesein vivodata were used to calibrate anH. pyloriinfection-dependent, CD4+T cell-specific computational model, which then described the mechanism by which IL-21 activates the production of interferon gamma (IFN-γ) and IL-17 during chronicH. pyloriinfection. The model predicted activated expression of T-bet and RORγt and the phosphorylation of STAT3 and STAT1 and suggested a potential role of IL-21 in the modulation of IL-10. Driven by our modeling-derived predictions, we found reduced levels of CD4+splenocyte-specifictbx21androrcexpression, reduced phosphorylation of STAT1 and STAT3, and an increase in CD4+T cell-specific IL-10 expression inH. pylori-infected IL-21-deficient mice. Our results indicate that IL-21 regulates Th1 and Th17 effector responses during chronicH. pyloriinfection in a STAT1- and STAT3-dependent manner, therefore playing a major role controllingH. pyloriinfection and gastritis.IMPORTANCEHelicobacter pyloriis the dominant member of the gastric microbiota in more than 50% of the world’s population.H. pyloricolonization has been implicated in gastritis and gastric cancer, as infection withH. pyloriis the single most common risk factor for gastric cancer. Current data suggest that, in addition to bacterial virulence factors, the magnitude and types of immune responses influence the outcome of colonization and chronic infection. This study uses a combined computational and experimental approach to investigate how IL-21, a proinflammatory T cell-derived cytokine, maintains the chronic proinflammatory T cell immune response driving chronic gastritis duringH. pyloriinfection. This research will also provide insight into a myriad of other infectious and immune disorders in which IL-21 is increasingly recognized to play a central role. The use of IL-21-related therapies may provide treatment options for individuals chronically colonized withH. pylorias an alternative to aggressive antibiotics.

scholarly journals MALT lymphoma: epidemiology, clinical diagnosis and treatment

2018 ◽  
Vol 11 (3) ◽  
pp. 187-193 ◽  
Author(s):  
Petruta Violeta Filip ◽  
◽  
Denisa Cuciureanu ◽  
Laura Sorina Diaconu ◽  
Ana Maria Vladareanu ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
B Cell ◽  
Malt Lymphoma ◽  
Cell Lymphoma ◽  
Gastric Lymphoma ◽  
Eradication Therapy ◽  
B Cell Lymphoma ◽  
Gastric Malt Lymphoma ◽  
H Pylori

Primary gastric lymphoma (PGL) represents a rare pathology, which can be easily misdiagnosed because of unspecific symptoms of the digestive tract. Histologically, PGL can vary from indolent marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue (MALT) to aggressive diffuse large B-cell lymphoma (DLBCL). During the years, clinical trials revealed the important role of Helicobacter pylori (H. pylori) in the pathogenesis of gastric MALT lymphoma. Infection with Helicobacter pylori is an influential promoter of gastric lymphomagenesis initiation. Long-term studies revealed that eradication therapy could regress gastric lymphomas.

scholarly journals Genotyping pattern of the vacuolating cytotoxin A and cytotoxin associated gene A of the Helicobacter pylori strains detected in fecal samples of household dogs

2017 ◽  
Vol 8 (2) ◽  
Author(s):  
Asieh Bolandi ◽  
Saam Torkan ◽  
Iman Alavi
Keyword(s):  
Helicobacter Pylori ◽  
16S Rrna ◽  
16S Rrna Gene ◽  
Pcr Amplification ◽  
Rrna Gene ◽  
Fecal Samples ◽  
The Status ◽  
Cytotoxin Associated Gene A ◽  
H Pylori

In despite of the high clinical impact of Helicobacter pylori, its exact sources and routes of transmission are unknown. Dogs may play an imperative role in the transmission of H. pylori to humans. The current investigation was done to study the status of vacA and cagA genotypes in the H. pylori strains of dogs. One-hundred and fifty fecal samples were collected from healthy and complicated household dogs. Genomic DNA was extracted from fecal samples and presence of 16S rRNA gene was studied using the PCR amplification. Distribution of vacA and cagA genotypes were studied by the multiplex PCR. Thirteen out of 150 fecal samples (8.66%) were positive for H. pylori 16S rRNA gene. Prevalence of H. pylori in healthy and complicated dogs were 5.55% and 8.57%, respectively. Male had the higher prevalence of H. pylori (P=0.038). The most commonly detected genotypes among the H. pylori strains were vacAs1A (61.53%), cagA (38.46%), vacAm1a (38.46%), vacAs2 (30.76%) and vacAm2 (30.76%). The most commonly detected combined genotypes were s1aCagA (30.76%), s1am1a (23.07%), s2m1a (23.07%) and s2CagA (23.07%). Iranian household dogs harbor H. pylori in their fecal samples similar in genotypes of the vacA and cagA alleles which suggest that complicated and even healthy dogs may be the latent host of the H. pylori and its genotypes. However, supplementary studies are required to found the exact role of dogs as a definitive host of the H. pylori.

scholarly journals Identification of Markers for Helicobacter pylori Strains Isolated from Children with Peptic Ulcer Disease by Suppressive Subtractive Hybridization

2006 ◽  
Vol 74 (7) ◽  
pp. 4064-4074 ◽  
Author(s):  
Mónica Oleastro ◽  
Lurdes Monteiro ◽  
Philippe Lehours ◽  
Francis Mégraud ◽  
Armelle Ménard
Keyword(s):  
Helicobacter Pylori ◽  
Peptic Ulcer ◽  
Peptic Ulcer Disease ◽  
Subtractive Hybridization ◽  
Suppressive Subtractive Hybridization ◽  
Ulcer Disease ◽  
Lipopolysaccharide Biosynthesis ◽  
The Difference ◽  
H Pylori

ABSTRACT Peptic ulcer disease (PUD) occurs after a long-term Helicobacter pylori infection. However, the disease can develop earlier, and rare cases have been observed in children, suggesting that these H. pylori strains may be more virulent. We used suppressive subtractive hybridization for comparative genomics between H. pylori strains isolated from a 5-year-old child with duodenal ulcer and from a sex- and age-matched child with gastritis only. The prevalence of the 30 tester-specific subtracted sequences was determined on a collection of H. pylori strains from children (15 ulcers and 30 gastritis) and from adults (46 ulcers and 44 gastritis). Two of these sequences, jhp0562 (80.0% versus 33.3%, P = 0.008) and jhp0870 (80.0% versus 36.7%, P = 0.015), were highly associated with PUD in children and a third sequence, jhp0828, was less associated (40.0% versus 10.0%, P = 0.048). Among adult strains, none of the 30 sequences was associated with PUD. However, both jhp0562 and jhp0870 were less prevalent in adenocarcinoma strains than in PUD strains from children and adults, the difference being statistically significant for jhp0870. In conclusion, two H. pylori genes were identified as being strongly associated with PUD in children, and their putative roles as an outer membrane protein for jhp0870 and in lipopolysaccharide biosynthesis for jhp0562, suggest that they may be novel virulence factors of H. pylori.

scholarly journals Furazolidone- and Nitrofurantoin-ResistantHelicobacter pylori: Prevalence and Role of Genes Involved in Metronidazole Resistance

2001 ◽  
Vol 45 (1) ◽  
pp. 306-308 ◽  
Author(s):  
Dong H. Kwon ◽  
Miae Lee ◽  
J. J. Kim ◽  
J. G. Kim ◽  
F. A. K. El-Zaatari ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Clinical Isolates ◽  
Metronidazole Resistance ◽  
H Pylori

ABSTRACT The prevalence of furazolidone, nitrofurantoin, and metronidazole resistance among Helicobacter pylori strains was assessed with 431 clinical isolates. Fifty-two percent were metronidazole resistant, compared to 2% (7 of 431) with resistance to furazolidone and nitrofurantoin. All seven furazolidone- and nitrofurantoin-resistant isolates were also metronidazole resistant.rdxA, frxA, and fdxB knockouts did not result in furazolidone or nitrofurantoin resistance. These data suggest that furazolidone and nitrofurantoin may be good alternatives to metronidazole for treating H. pylori infection.

scholarly journals Effect of Helicobacter pylori on Polymorphonuclear Leukocyte Migration across Polarized T84 Epithelial Cell Monolayers: Role of Vacuolating Toxin VacA and cagPathogenicity Island

2000 ◽  
Vol 68 (9) ◽  
pp. 5225-5233 ◽  
Author(s):  
Véronique Hofman ◽  
Vittorio Ricci ◽  
Antoine Galmiche ◽  
Patrick Brest ◽  
Patrick Auberger ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Polymorphonuclear Leukocyte ◽  
Broth Culture ◽  
Intestinal Cell ◽  
T84 Cells ◽  
Vacuolating Cytotoxin ◽  
Intestinal Cell Line ◽  
H Pylori

ABSTRACT Helicobacter pylori infection can induce polymorphonuclear leukocyte (PMNL) infiltration of the gastric mucosa, which characterizes acute chronic gastritis. The mechanisms underlying this process are poorly documented. The lack of an in vitro model has considerably impaired the study of transepithelial migration of PMNL induced by H. pylori. In the present work, we used confluent polarized monolayers of the human intestinal cell line T84 grown on permeable filters to analyze the epithelial PMNL response induced by broth culture filtrates (BCFs) and bacterial suspensions from different strains of H. pylori. We have evaluated the role of the vacuolating cytotoxin VacA and of the cagpathogenicity island (PAI) of H. pylori in PMNL migration via their effects on T84 epithelial cells. We noted no difference in the rates of PMNL transepithelial migration after epithelial preincubation with bacterial suspensions or with BCFs of VacA-negative or VacA-positive H. pylori strains. In contrast, PMNL transepithelial migration was induced after incubation of the T84 cells with cag PAI-positive and cagE-positiveH. pylori strains. Finally, PMNL migration was correlated with a basolateral secretion of interleukin-8 by T84 cells, thus creating a subepithelial chemotactic gradient for PMNL. These data provide evidence that the vacuolating cytotoxin VacA is not involved in PMNL transepithelial migration and that the cag PAI, with a pivotal role for the cagE gene, provokes a transcellular signal across T84 monolayers, inducing a subepithelial PMNL response.

scholarly journals OX40L/OX40 Signal Promotes IL-9 Production by Mucosal MAIT Cells During Helicobacter pylori Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Siqi Ming ◽  
Mei Zhang ◽  
Zibin Liang ◽  
Chunna Li ◽  
Jianzhong He ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Potential Role ◽  
Critical Role ◽  
Underlying Mechanism ◽  
Mucosal Inflammation ◽  
Cross Linking ◽  
Mait Cells ◽  
H Pylori ◽  
Mait Cell

Mucosal associated invariant T (MAIT) cells play a critical role in Helicobacter pylori (H. pylori)-induced gastritis by promoting mucosal inflammation and aggravating mucosal injuries (1, 2). However, the underlying mechanism and key molecules involved are still uncertain. Here we identified OX40, a co-stimulatory molecule mainly expressed on T cells, as a critical regulator to promote proliferation and IL-9 production by MAIT cells and facilitate mucosal inflammation in H. pylori-positive gastritis patients. Serum examination revealed an increased level of IL-9 in gastritis patients. Meanwhile, OX40 expression was increased in mucosal MAIT cells, and its ligand OX40L was also up-regulated in mucosal dendritic cells (DCs) of gastritis patients, compared with healthy controls. Further results demonstrated that activation of the OX40/OX40L pathway promoted IL-9 production by MAIT cells, and MAIT cells displayed a highly-activated phenotype after the cross-linking of OX40 and OX40L. Moreover, the level of IL-9 produced by MAIT cells was positively correlated with inflammatory indexes in the gastric mucosa, suggesting the potential role of IL-9-producing MAIT cells in mucosal inflammation. Taken together, we elucidated that OX40/OX40L axis promoted mucosal MAIT cell proliferation and IL-9 production in H. pylori-induced gastritis, which may provide potential targeting strategies for gastritis treatment.

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