A standardized mouse model of Helicobacter pylori infection: Introducing the Sydney strain

Lee, A; O’Rourke, Jani; Ungria, Maria Corazon A. De; Robertson, Bronwyn R.; Daskalopoulos, George; Dixon, M. F.

doi:10.1016/s0016-5085(97)70155-0

Cited by 864 publications

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“…Lack of protective immune responses after prophylactic vaccination of CD4 1 T-cell-deficient mice C57BL/6 or CD4 1 T-cell-deficient C57BL/6.BM1.GK 1.5 (GK1.5 mice) [21] mice were vaccinated with a single oral dose of recombinant S. Typhimurium expressing H. pylori ureA&B (SL3261 pYZ97) [22], or the carrier (SL3261) and challenged 4 wk later with a single dose of H. pylori Sydney strain 1 (SS1, a mouse-adapted strain) [23]. Three, seven and 21 days after challenge infection, mice were euthanised, stomachs were homogenised and levels of colonisation were determined by quantitative culture and expressed as Log 10 CFU per g tissue.…”

Section: Resultsmentioning

confidence: 99%

Local recall responses in the stomach involving reduced regulation and expanded help mediate vaccine‐induced protection against Helicobacter pylori in mice

Becher¹,

Deutscher²,

Simpfendorfer³

et al. 2010

Eur J Immunol

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Helicobacter pylori is recognised as the chief cause of chronic gastritis, ulcers and gastric cancer in humans. With increased incidence of treatment failure and antibiotic resistance, development of prophylactic or therapeutic vaccination is a desirable alternative. Although the results of vaccination studies in animal models have been promising, studies in human volunteers have revealed problems such as 'post-immunisation gastritis' and comparatively poor responses to vaccine antigens. The focus of this study was to compare the gastric and systemic cellular immune responses induced by recombinant attenuated Salmonella Typhimurium-based vaccination in the C57BL/6 model of H. pylori infection. Analysis of lymphocyte populations in the gastric mucosa, blood, spleen, paragastric LN and MLN revealed that the effects of vaccination were largely confined to the parenchymal stomach rather than lymphoid organs. Vaccine-induced protection was correlated with an augmented local recall response in the gastric mucosa, with increased proportions of CD4 1 T cells, neutrophils and reduced proportions of CD4 1 Treg. CD4 1 T cells isolated from the stomachs of vaccinated mice proliferated ex vivo in response to H. pylori antigen, and secreted Th1 cytokines, particularly IFN-c. This detailed analysis of local gastric immune responses provides insight into the mechanism of vaccine-induced protection.Key words: Helicobacter pylori . Stomach . Treg cells . Vaccine IntroductionHelicobacter pylori is a Gram-negative spiral bacterium that infects the mucous gel layer of the human stomach. Infection is chronic and causes a range of diseases ranging from acute to chronic gastritis, ulcers and, in a small proportion of patients, gastric adenocarcinoma [1].The treatment of H. pylori disease is not straightforward. The most commonly used combination antibiotic therapy, amoxicillin plus clathromycin and a proton pump inhibitor, now only achieve a cure in o80% of cases [2]. This efficacy rate is substantially less than the 495% rate that is deemed acceptable for most other infectious diseases. A prophylactic or therapeutic vaccine would be a cost-effective way to control H. pylori-induced disease.Vaccination is effective in animal models, with 10-to 100-fold reductions (but not sterile immunity) in bacterial colonisation reported in a variety of experimental animals, following immunisation by either oral or parenteral routes (reviewed in [3][4][5]). Oral (mucosal route) vaccination is desirable for a human H. pylori vaccine because of the ease of delivery and, for a live vaccine, the necessity of a single dose is also attractive. 2778with issues such as poor immunogenicity [6], and adverse reactions [7], presenting serious obstacles to further progression of a human vaccine [8]. The reasons for this failure probably result from apparently opposing aspects of the immune response to vaccination. On the one hand vaccination causes 'post-immunisation gastritis' a local inflammatory responses in the stomach in many animal and human recipients, a...

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Section: Resultsmentioning

confidence: 99%

Local recall responses in the stomach involving reduced regulation and expanded help mediate vaccine‐induced protection against Helicobacter pylori in mice

Becher¹,

Deutscher²,

Simpfendorfer³

et al. 2010

Eur J Immunol

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“…Helicobacter strains used for animal experimentation were H. felis CS1 (ATCC 49179) 19 and H. pylori strain SS1. 20 Mouse infections were performed orally with ~10 8 bacteria. Primary gastric epithelial cells were isolated as previously described; 21 the immortalized murine gastric epithelial cell line used in this study was also described previously.…”

Section: Mice Cell Culture Bacterial Infections and Vaccinationmentioning

confidence: 99%

Prostaglandin E2 Prevents Helicobacter-Induced Gastric Preneoplasia and Facilitates Persistent Infection in a Mouse Model

et al. 2010

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“…pylori wild-type strain SS1 was used in this study [12]. Defined isogenic H. pylori SS1 mutants were constructed as described previously [13].…”

Section: Construction Of Defined Isogenic H Pylori Mutantsmentioning

confidence: 99%

Helicobacter pylori adherence to gastric epithelial cells: a role for non-adhesin virulence genes

Zhang¹,

Dorrell

Wren

et al. 2002

Journal of Medical Microbiology

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Helicobacter pylori is a major aetiological agent in gastroduodenal disorders and adherence of the bacteria to the gastric mucosa is one of the initial stages of infection. Although a number of specific adhesins has been identified, other H. pylori virulence factors may play a role in adherence to gastric epithelial cells directly or through interaction with other adhesins. This study assessed the effect of 16 H. pylori virulence factors on the adherence of the bacteria to gastric AGS cells and on gastric epithelial cell cycle distribution. Defined isogenic H. pylori SS1 mutants were used. After coincubation of gastric AGS cells and bacteria, adherence of H. pylori to AGS cells was visualised by immunofluorescence microscopy and quantified by flow cytometry. Cell cycle phase distribution was analysed by flow cytometry with propidium iodide staining. Mutants were tested for their ability to adhere to AGS cells and compared with the wild-type SS1 strain. Mutations in genes in the cag pathogenicity island showed that cagP and cagE mutants adhered less than the wild-type strain to AGS cells, whereas a cagF mutant showed no reduction in adherence. Mutations in genes involved in flagellar biosynthesis showed that the adherence ability of fliQ, f liM and fliS mutants was reduced, but a flhB mutant possessed wild-type levels of adherence. Mutations in genes coding for the urease (ureB) and phospholipase (pldA) enzymes did not affect adherence, but mutation of the tlyA gene encoding an H. pylori haemolysin resulted in a reduced adherence. A fliQ mutant, with reduced adherence to AGS cells, was less able to induce AGS cell apoptosis than SS1. The ability to induce G 0 G 1 cell cycle arrest was also abolished in the fliQ mutant. However, an increased cell number in S phase was observed when AGS cells were exposed to the fliQ mutant compared with SS1, suggesting that unattached bacteria may still be able to stimulate cell proliferation. In addition to known adhesins, other bacterial virulence factors such as CagE, CagP, FliQ, FliM, FliS and TlyA appear to play a role in H. pylori adherence to gastric epithelial cells. Mutations in these genes may affect H. pylori pathogenicity by reducing either the ability of the bacteria to attach to gastric epithelial cells or the intensity of bacteriahost cell interactions.

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A standardized mouse model of Helicobacter pylori infection: Introducing the Sydney strain

Cited by 864 publications

References 1 publication

Local recall responses in the stomach involving reduced regulation and expanded help mediate vaccine‐induced protection against Helicobacter pylori in mice

Local recall responses in the stomach involving reduced regulation and expanded help mediate vaccine‐induced protection against Helicobacter pylori in mice

Prostaglandin E2 Prevents Helicobacter-Induced Gastric Preneoplasia and Facilitates Persistent Infection in a Mouse Model

Helicobacter pylori adherence to gastric epithelial cells: a role for non-adhesin virulence genes

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