<i>Helicobacter pylori</i>-Specific Antibodies Impair the Development of Gastritis, Facilitate Bacterial Colonization, and Counteract Resistance against Infection

Akhiani, Ali A.; Schön, Karin; Franzén, Lennart; Pappo, Jacques; Lycke, Nils

doi:10.4049/jimmunol.172.8.5024

Cited by 94 publications

(101 citation statements)

References 78 publications

(100 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Studies have suggested that locally produced antibodies, particularly IgA [13,14], might block H. pylori infection by preventing colonization and adhesion and allowing killing by neutrophils or monocytes through bacterial opsonisation [15,16]. Helicobacter-specific IgA monoclonal antibodies administered directly into the gastric lumen conferred protection against H. felis infection [11,17] and neutralized the toxic products of Helicobactor pylori [18]. The results of present study are in accordance with favourable role indicated in the above mentioned studies.…”

Section: Discussionsupporting

confidence: 89%

“…However, even though H. pylori infection stimulates strong local and systemic specific IgA and IgG antibody production, it is still controversial as to what influence antibodies may have on the bacterial colonization [7][8][9]. While earlier reports claimed eradication as well as protection from the infection by H. felis by active oral and passive IgA immunization [8,10], another study claims that antibodies were not only dispensable for protection, but also impaired elimination of bacteria and the development of gastric inflammation [11].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Mucosal IgA & IL-1β in Helicobacter pylori Infection

et al. 2012

View full text Add to dashboard Cite

Helicobacter pylori infection stimulates strong local inflammatory and specific IgA antibody production. The influence of antibodies on the bacterial colonization is not clear. Here, we have analysed the association between the mucosal IgA level and IL-1b in various manifestations of the infection seen endoscopically. Antral biopsies of 57 dyspeptic patients were taken for culture, histology and estimation of mucosal levels of anti-H. pylori IgA and IL1b. Mean mucosal IgA level was higher in patients with normal mucosa compared to all other groups and lower IgA level was associated with higher bacterial density. IL-1b was higher in ulcer patients and suspicious malignancy group as compared to normal group and higher level of IL-1b was associated with higher grades of metaplasia. Present study indicates that local immunity seems to have a protective role against H. pylori infection and higher level of IL-1b induced by the pathogen may be associated with metaplasia and carcinogenesis.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Mucosal IgA & IL-1β in Helicobacter pylori Infection

et al. 2012

View full text Add to dashboard Cite

show abstract

“…In contrast, Th2 cells do not appear to be needed for protection, but they may contribute to the severity of postimmunization gastritis, as suggested by observations made in IL-4-deficient mice (18,20). Moreover, Th2 cells increase in number in well-protected mice over time after immunization, perhaps indicating a role in long term protection (6,11). Thus, both Th1 and Th2 cells could be involved in the development of immune protection against H. pylori (11, 21).…”

Section: Vaccine-induced Immunity Against Helicobacter Pylorimentioning

confidence: 82%

“…Thus, both Th1 and Th2 cells could be involved in the development of immune protection against H. pylori (11, 21). These observations, in addition to the dominance of eosinophilic cells in well-protected gastric mucosa, suggest a common regulatory link between Th1-and Th2-dependent functions, promoting resistance to H. pylori infection (6,12). One factor that could fulfill such a role is IL-18, which is known to affect Th1 development/IFN-␥ production as well as influence Th2-controled functions (22,23).…”

Section: Vaccine-induced Immunity Against Helicobacter Pylorimentioning

confidence: 99%

Vaccine-Induced Immunity againstHelicobacter pyloriInfection Is Impaired in IL-18-Deficient Mice

Akhiani

Schön

Lycke

2004

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Protective immunity against Helicobacter pylori infection in mice has been associated with a strong Th1 response, involving IL-12 as well as IFN-γ, but recent studies have also demonstrated prominent eosinophilic infiltration, possibly linked to local Th2 activity in the gastric mucosa. In this study we investigated the role of IL-18, because this cytokine has been found to be a coregulator of Th1 development as well as involved in Th2-type responses with local eotaxin production that could influence gastric eosinophilia and resistance to infection. We found that IL-18−/− mice failed to develop protection after oral immunization with H. pylori lysate and cholera toxin adjuvant, indicating an important role of IL-18 in protection. Well-protected C57BL/6 wild-type (WT) mice demonstrated substantial influx of CD4+ T cells and eosinophilic cells in the gastric mucosa, whereas IL-18−/− mice had less gastritis, few CD4+ T cells, and significantly reduced numbers of eosinophilic cells. T cells in well-protected WT mice produced increased levels of IFN-γ and IL-18 to recall Ag. By contrast, unprotected IL-18−/− mice exhibited significantly reduced gastric IFN-γ and specific IgG2a Ab levels. Despite differences in gastric eosinophilic cell infiltration, protected WT and unprotected IL-18−/− mice had comparable levels of local eotaxin, suggesting that IL-18 influences protection via Th1 development and IFN-γ production rather than through promoting local production of eotaxin and eosinophilic cell infiltration.

show abstract

“…However, the key role of Th1 cells in inducing the secretion of IgG by activated plasma cells or the activation of macrophage killing appear to be dispensable for protection [37][38][39]. Immunity might be facilitated by as yet unknown effector mechanisms and it is important to explore novel cell types or molecules in immunity to this end.…”

Section: Discussionmentioning

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

View full text Add to dashboard Cite

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...

show abstract

Helicobacter pylori-Specific Antibodies Impair the Development of Gastritis, Facilitate Bacterial Colonization, and Counteract Resistance against Infection

Cited by 94 publications

References 78 publications

Mucosal IgA & IL-1β in Helicobacter pylori Infection

Mucosal IgA & IL-1β in Helicobacter pylori Infection

Vaccine-Induced Immunity againstHelicobacter pyloriInfection Is Impaired in IL-18-Deficient Mice

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

Contact Info

Product

Resources

About