Macrophages Are Mediators of Gastritis in Acute Helicobacter pylori Infection in C57BL/6 Mice

ABSTRACT Helicobacter pylori is the etiological agent of human chronic gastritis, a condition seen as a precursor to the development of gastrointestinal ulcers or gastric cancer. This study utilized the murine model of chronic H. pylori infection to characterize the role of macrophages in the induction of specific immune responses and gastritis and in the control of the bacterial burden following H. pylori infection and vaccination. Drug-loaded liposomes were injected intravenously to deplete macrophages from C57BL/6 mice, and effective removal of CD11b+ cells from the spleens and stomachs of mice was confirmed by immunofluorescence microscopy. Transient elimination of macrophages from C57BL/6 mice during the early period of infection reduced the gastric pathology induced by H. pylori SS1 but did not affect the bacterial load in the stomach. These data suggest that macrophages are important to the severity of gastric inflammation during H. pylori infection.

Download Full-text

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

mBio ◽

10.1128/mbio.01243-14 ◽

2014 ◽

Vol 5 (4) ◽

Cited By ~ 36

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.

Download Full-text

Helicobacter pylori bacteremia: an unusual finding

Infectious Disease Reports ◽

10.4081/idr.2016.6612 ◽

2016 ◽

Vol 8 (3) ◽

Author(s):

Concetta De Luca ◽

Annalisa Mancin ◽

Maria Calabrò ◽

Cristina Daleno ◽

Antonella Ferrario ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Potential Role ◽

Rare Complication ◽

Subtotal Gastrectomy ◽

Blood Cultures ◽

H Pylori ◽

Stomach Surgery ◽

Unusual Finding

We report a case of Helicobacter pylori transient bacteremia in a woman with ulcerated antral gastric cancer. The patient was hospitalized for laparoscopy and subtotal gastrectomy. After surgery she developed fever (39°C) and was empirically treated with levofloxacin. Blood cultures, collected and sent immediately to Laboratory, were positive for a spiral Gramnegative bacterium. This isolate was identified as H. pylori and the specific susceptibility test was performed. One day after the fever was decreased but antibiotic treatment with levofloxacin was continued and it was maintained until discharge. In summary, H. pylori transient bacteremia may occur as a rare complication after stomach surgery. Further studies are necessary to elucidate the potential role of H. pylori presence in blood.

Download Full-text

Los genes como marcadores de riesgo en cáncer gástrico: revisión de estudios en población colombiana

Respuestas ◽

10.22463/0122820x.383 ◽

2013 ◽

Vol 18 (2) ◽

pp. 61-73

Author(s):

Claudia Marcela Yáñez-Gutiérrez

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Gene Polymorphisms ◽

Genetic Factors ◽

Human Gene ◽

Risk Markers ◽

Different Populations ◽

H Pylori ◽

Cáncer Gástrico

El objetivo de esta revisión, fue identificar el rol de los genes como marcadores de riesgo en cáncer gástrico (CG) en población colombiana. Se revisaron publicaciones de investigaciones realizadas en los últimos diez años, utilizando las bases MEDLINE y LILACS y complementando la pesquisa con la bibliografía relevante de los artículos. Se encontraron estudios en busca de asociación de CG con polimorfismos de varios genes humanos involucrados en la respuesta inmune, la desintoxicación y el supresor p53. En Colombia al igual que en otros países, las evidencias de asociación de polimorfismos genéticos con CG son aún controversiales, debido a la variación de los resultados que arrojan los estudios en las diferentes poblaciones. El genoma de las cepas de Helicobacter pylori que infectan población colombiana también ha sido investigado en búsqueda de polimorfismos de virulencia. El genotipo cagA/vacAs1m1 identificado como citotóxico en esta bacteria, mostró en la mayoría de las investigaciones, asociación con CG. La evidencia de asociación de CG con factores genéticos en población colombiana no es concluyente. Está lejos aún, la identificación de marcadores genéticos que permitan predecir el riesgo a desarrollar CG. A pesar de ello, algunos polimorfismos de genes humanos como los de IL-1 o los de algunas enzimas desintoxicantes, así como los genes cagA y vacA de Helicobacter pylori podrían ser candidatos a futuros marcadores de riesgo en esta neoplasia.Palabras clave: cáncer gástrico, riesgo, genotipo, Colombia. ABSTRACT The objective of this review was to identify the role of genes as risk markers in gastric cancer (GC) in Colombian population studies. The study reviewed research publications in the last ten years, using the MEDLINE and LILACS, as well as various literature research of relevant articles. Searching studies found GC association with several human gene polymorphisms involved in the immune response, detoxification and suppressor p53. In Colombia, as in other countries, the evidence of the association of genetic polymorphisms with GC are still controversial because of the variation in results that studies in different populations. The genome of Helicobacter pylori strains that infect Colombian population has also been investigated in search of polymorphisms of virulence. cagA/ vacAs1m1 genotype identified as cytotoxic in this bacterium, demonstrated most of the research associated with GC. Evidence of association of GC with Colombian population genetic factors was inconclusive. It is yet to be determined the exact identification of genetic markers that can predict the risk of developing GC. However, some human gene polymorphisms as IL-1 or some detoxifying enzymes and the vacA and cagA of H. pylori could be candidates for future risk markers in these tumors.Keywords: gastric cancer, risk, genotype, Colombia

Download Full-text

Three-decade failure to eradication of refractory Helicobacter pylori infec-tion and recent efforts to eradicate the infection

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200807110849 ◽

2020 ◽

Vol 21 ◽

Author(s):

Majid Taati Moghadam ◽

Zahra Chegini ◽

Amin Norouzi ◽

Amin Sadeghi Dosari ◽

Aref Shariati

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Bacterial Load ◽

Duodenal Ulcers ◽

The Future ◽

Patient Cooperation ◽

Dormant Forms ◽

Stomach Ph ◽

High Bacterial Load ◽

H Pylori

Background: Helicobacter pylori causes dangerous and deadly diseases such as gastric cancer and duodenal ulcers. Eradication and treatment of this bacterium are very important due to the deadly diseases caused by H. pylori and the high cost of treatment for countries. So, we present a complete list of the most important causes of failure in the treatment and eradication of H. pylori, and addresses new therapeutic methods that may be effective in controlling this bacterium in the future. Results: Many efforts have been made to control and eradicate this bacterium over the years, but no success has been achieved since its eradication is a complex process affected by the bacterial properties and host factors. Previous studies have shown that various factors are involved in failure to eradicate H. pylori, such as new genotypes of the bacterium with higher pathogenicity, inappropriate patient cooperation, mutations, biofilm formation and dormant forms that cause antibiotic resistance, acidic stomach pH, high bacterial load, smoking, immunosuppressive features and intracellular occurrence of H. pylori. On the other hand, recent studies reported that the use of probiotics, nanoparticles, antimicrobial peptides, natural product and vaccine can be helpful in the treatment and eradication of H. pylori infections. Conclusion: Eradication of H. pylori is crucial for the treatment of important diseases such as gastric cancer. Therefore, it seems that identifying the failure causes of treating this bacterium can be helpful in controlling the infections. Besides, further studies on new therapeutic strategies may help eradicate H. pylori in the future.

Download Full-text

The Human Gastric Pathogen Helicobacter pylori and Its Association with Gastric Cancer and Ulcer Disease

Ulcers ◽

10.1155/2011/340157 ◽

2011 ◽

Vol 2011 ◽

pp. 1-23 ◽

Cited By ~ 58

Author(s):

Bianca Bauer ◽

Thomas F. Meyer

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Peptic Ulcer ◽

Peptic Ulcer Disease ◽

Strain Differences ◽

Protective Effects ◽

Ulcer Disease ◽

Prophylactic Measures ◽

H Pylori

With the momentous discovery in the 1980's that a bacterium, Helicobacter pylori, can cause peptic ulcer disease and gastric cancer, antibiotic therapies and prophylactic measures have been successful, only in part, in reducing the global burden of these diseases. To date, ~700,000 deaths worldwide are still attributable annually to gastric cancer alone. Here, we review H. pylori's contribution to the epidemiology and histopathology of both gastric cancer and peptic ulcer disease. Furthermore, we examine the host-pathogen relationship and H. pylori biology in context of these diseases, focusing on strain differences, virulence factors (CagA and VacA), immune activation and the challenges posed by resistance to existing therapies. We consider also the important role of host-genetic variants, for example, in inflammatory response genes, in determining infection outcome and the role of H. pylori in other pathologies—some accepted, for example, MALT lymphoma, and others more controversial, for example, idiopathic thrombocytic purpura. More recently, intriguing suggestions that H. pylori has protective effects in GERD and autoimmune diseases, such as asthma, have gained momentum. Therefore, we consider the basis for these suggestions and discuss the potential impact for future therapeutic rationales.

Download Full-text

Helicobacter pylori Eradication in Patients Undergoing Gastrectomy: Diagnosis and Therapy

The Korean Journal of Helicobacter and Upper Gastrointestinal Research ◽

10.7704/kjhugr.2019.0037 ◽

2020 ◽

Vol 20 (3) ◽

pp. 204-209

Author(s):

Youn I Choi ◽

Jun-Won Chung

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Diagnostic Tests ◽

Remnant Stomach ◽

Optimal Timing ◽

Helicobacter Pylori Eradication ◽

Metachronous Gastric Cancer ◽

H Pylori

The role of Helicobacter pylori (H. pylori) eradication in patients undergoing gastrectomy for gastric cancer is unclear. Although European and Asian guidelines strongly recommend H. pylori eradication in patients who undergo endoscopic resection for early gastric cancer, these guidelines do not specify the tests useful for diagnosing H. pylori infection, the optimal timing and appropriate eradication regimens, and follow-up strategies in patients undergoing gastrectomy for gastric cancer. This review aims to update the guidelines for the diagnosis and management of H. pylori infection in patients undergoing gastrectomy for gastric cancer. We have focused on the following issues: 1) diagnostic tests for H. pylori infection in the remnant stomach, 2) optimal timing and regimen for H. pylori eradication, and 3) role of H. pylori eradication in reducing the risk of metachronous gastric cancer in the remnant stomach.

Download Full-text

Gastric Cancer and Associated Pathogens: Is There Any Association in Moroccan Region?

10.21203/rs.3.rs-1169749/v1 ◽

2021 ◽

Author(s):

Samia Alaoui Boukhris ◽

Mounia El khadir ◽

Safae Karim ◽

Tiatou Souho ◽

Dafr-Allah Benajah ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Retrospective Study ◽

Epstein Barr Virus ◽

University Hospital ◽

Cancer Development ◽

Barr Virus ◽

Epstein Barr ◽

H Pylori

Abstract Purpose: Helicobacter pylori, Epstein-Barr virus and human papillomavirus are three pathogens associated with various human cancers. This study aimed to investigate the role of these pathogens in gastric cancer in Moroccan population Methods: For this, a retrospective study has been conducted on participants attending the gastroenterology department of Hassan II University Hospital of Fez. A total of 279 participants were enrolled. H. pylori, EBV and HPV were detected and genotyped by PCR.Results: A significant association has been established between H. pylori, EBV and gastric cancer. 93.4% and 43.3% of gastric cancer cases are related to H. pylori and EBV respectively (p≤0.01). H. pylori-EBV co-infection is responsible of 31.6% of gastric cancer cases (p<0.01). Correlation between pathogens genotypes and gastric cancer shows 55.6% of GC EBV positives are carrying the 30bp deletion in LMP1gene, while 16% of gastric cancers cases are carrying high-risk genotypes of HPV (p=0.21). Conclusion: The obtained results highlight the possible role of co-infection in gastric cancer development.

Download Full-text

A Double Mutant Heat-Labile Toxin from Escherichia coli, LT(R192G/L211A), Is an Effective Mucosal Adjuvant for Vaccination against Helicobacter pylori Infection

Infection and Immunity ◽

10.1128/iai.01407-12 ◽

2013 ◽

Vol 81 (5) ◽

pp. 1532-1540 ◽

Cited By ~ 52

Author(s):

Louise Sjökvist Ottsjö ◽

Carl-Fredrik Flach ◽

John Clements ◽

Jan Holmgren ◽

Sukanya Raghavan

Keyword(s):

Escherichia Coli ◽

Helicobacter Pylori ◽

Immune Responses ◽

Double Mutant ◽

Bacterial Load ◽

Mucosal Vaccine ◽

Mucosal Adjuvant ◽

Content Type ◽

Heat Labile ◽

H Pylori

ABSTRACTHelicobacter pyloriinfection in the stomach is a common cause of peptic ulcer disease and is a strong risk factor for the development of gastric adenocarcinoma, yet no effective vaccine againstH. pyloriinfection is available to date. In mice, mucosal vaccination withH. pyloriantigens when given together with cholera toxin (CT) adjuvant, but not without adjuvant, can induce protective immune responses againstH. pyloriinfection. However, the toxicity of CT precludes its use as a mucosal adjuvant in humans. We evaluated a recently developed, essentially nontoxic double mutantEscherichia coliheat-labile toxin, LT(R192G/L211A) (dmLT), as a mucosal adjuvant in an experimentalH. pylorivaccine and compared it to CT in promoting immune responses and protection againstH. pyloriinfection in mice. Immunization via the sublingual or intragastric route withH. pylorilysate antigens and dmLT resulted in a significant decrease in bacterial load after challenge compared to that in unimmunized infection controls and to the same extent as when using CT as an adjuvant. Cellular immune responses in the sublingually immunized mice known to correlate with protection were also fully comparable when using dmLT and CT as adjuvants, resulting in enhancedin vitroproliferative and cytokine responses from spleen and mesenteric lymph node cells toH. pyloriantigens. Our results suggest that dmLT is an attractive adjuvant for inclusion in a mucosal vaccine againstH. pyloriinfection.

Download Full-text

Peptidoglycan Deacetylation in Helicobacter pylori Contributes to Bacterial Survival by Mitigating Host Immune Responses

Infection and Immunity ◽

10.1128/iai.00307-10 ◽

2010 ◽

Vol 78 (11) ◽

pp. 4660-4666 ◽

Cited By ~ 35

Author(s):

Ge Wang ◽

Susan E. Maier ◽

Leja F. Lo ◽

George Maier ◽

Shruti Dosi ◽

...

Keyword(s):

Oxidative Stress ◽

Helicobacter Pylori ◽

Immune Responses ◽

Bacterial Load ◽

Host Cells ◽

Infection Model ◽

Wild Type ◽

Mouse Infection Model ◽

Mouse Infection ◽

H Pylori

ABSTRACT An oxidative stress-induced enzyme, peptidoglycan deacetylase (PgdA), in the human gastric pathogen Helicobacter pylori was previously identified and characterized. In this study, we constructed H. pylori pgdA mutants in two mouse-adapted strains, X47 and B128, to investigate the role of PgdA in vivo (to determine the mutants’ abilities to colonize mice and to induce an immune response). H. pylori pgdA mutant cells showed increased sensitivity to lysozyme compared to the sensitivities of the parent strains. We demonstrated that the expression of PgdA was significantly induced (3.5-fold) when H. pylori cells were in contact with macrophages, similar to the effect observed with oxidative stress as the environmental inducer. Using a mouse infection model, we first examined the mouse colonization ability of an H. pylori pgdA mutant in X47, a strain deficient in the major pathway (cag pathogenicity island [PAI] encoded) for delivery of peptidoglycan into host cells. No animal colonization difference between the wild type and the mutant was observed 3 weeks after inoculation. However, the pgdA mutant showed a significantly attenuated ability to colonize mouse stomachs (9-fold-lower bacterial load) at 9 weeks postinoculation. With the cag PAI-positive strain B128, a significant colonization difference between the wild type and the pgdA mutant was observed at 3 weeks postinoculation (1.32 × 104 versus 1.85 × 103 CFU/gram of stomach). To monitor the immune responses elicited by H. pylori in the mouse infection model, we determined the concentrations of cytokines present in mouse sera. In the mice infected with the pgdA mutant strain, we observed a highly significant increase in the level of MIP-2. In addition, significant increases in interleukin-10 and tumor necrosis factor alpha in the pgdA mutant-infected mice compared to the levels in the wild-type H. pylori-infected mice were also observed. These results indicated that H. pylori peptidoglycan deacetylation is an important mechanism for mitigating host immune detection; this likely contributes to pathogen persistence.

Download Full-text

Helicobacter Pylori Infection And Gastric Cancer: Is It Our National Problem?

Journal of Bangladesh College of Physicians and Surgeons ◽

10.3329/jbcps.v36i2.36069 ◽

2018 ◽

Vol 36 (2) ◽

pp. 70-76 ◽

Cited By ~ 1

Author(s):

M Mizanur Rahman ◽

Shahjadul Alam ◽

Abu Mohammad Khaled Iqbal ◽

Md Monoar Hossain ◽

Abu Mohammad Kawser Sarker ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Current Knowledge ◽

Large Body ◽

High Prevalence ◽

The World ◽

Leading Position ◽

The Common ◽

H Pylori

Gastric cancer is a leading cause of cancer death worldwide. In Bangladesh it ranks a leading position among the cancers patients. A large body of evidence supports a causal role of Helicobacter pylori in the majority of gastric malignancies. Scientists throughout the world explored and reached to the understanding about the pathogenesis of their relationship, but much remains to be learned. Moreover, because of the high prevalence of infection, the lack of definitive trials, and the challenges of H. pylori treatment, there remains a debate regarding the consensus on the role of routine screening and treatment of this infection to prevent cancer. This article reviews the current knowledge on H. pylori and its role for gastric cancer, present status of Bangladesh and a recommendation for reduction of the infectivity among the common population.J Bangladesh Coll Phys Surg 2018; 36(2): 70-76

Download Full-text