Naturally acquired human immune responses against<i>Helicobacter pylori</i> and implications for vaccine development

Zevering, Yinka; Jacob, L.; Meyer, Thomas

doi:10.1136/gut.45.3.465

Cited by 55 publications

(45 citation statements)

References 126 publications

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“…127 More recently, several laboratories have shown that biopsies from gastric mucosa of normal, infected, and uninfected patients, revealed no or very low levels of mRNA of the classic Th2 cytokine IL-4. 137,138 These studies support the notion that most infected humans have a Th1 response, which does not eradicate H. pylori infection. It is therefore predictable that a Th2 response would be more effective.…”

Section: Vaccination Development For Clinical Use and Future Of The Hmentioning

confidence: 66%

“…In contrast, Th2 cells produce cytokines, which are responsible for eosinophil activation, inhibition of several macrophage functions that provide phagocyte-independent protective responses, and strong antibody production, particularly IgA and IgG, which are especially active on mucosal surfaces. 137,138 In the stomach, IL-12 and IL-10 production has been implicated in the selection of Th1 and Th2 cells, respectively. The relative predominance of IL-12 in the human stomach, regardless of whether it is infected or not, favors the development of a subset of helper T cells that tend to produce interferon gamma, which is associated with Th1 cells and enhanced cell-mediated immunity.…”

Section: Vaccination Development For Clinical Use and Future Of The Hmentioning

confidence: 99%

See 1 more Smart Citation

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

Aguilar¹,

Ayala²,

Fierros-Zarate³

2001

Salud pública Méx

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Helicobacter pylori has acquired great importance during the last two decades, after being recognized as an important pathogen that infects a great portion of the human population. This microorganism is recognized as the main causal agent of chronic gastritis and duodenal ulcers, and it is associated with the subsequent development of gastric carcinoma. The pathogenic mechanisms of H. pylori and their relation to gastric ailments have not been clearly defined. However, at present it is well established that urease, vacuolating cytotoxin VacA, and the pathogenicity island (cag PAI) gene products, are the main factors of virulence of this organism. Thus, individuals infected with strains that express these virulence factors probably develop a severe local inflammation that may induce the development of peptic ulcer and gastric cancer. The way the infection spreads throughout the world suggests the possibility that there are multiple pathways of transmission. Due to the importance that H. pylori has acquired as a human pathogen, laboratories worldwide are attempting to develop a vaccine that confers long-term immunological protection against infection by this microorganism. Hence, the objective of this review is to present the most relevant findings of the biology of H. Pylori and its interaction with the human host. The full version of this paper is available too at: http:// www.insp.mx/salud/index.html ResumenHelicobacter pylori ha adquirido gran importancia durante las últimas dos décadas, al ser reconocido como un importante patógeno que infecta una gran porción de la población humana. Este microrganismo es reconocido como el principal agente que causa la gastritis crónica y la úlcera duodenal, además de que se ha asociado con el subsecuente desarrollo del carcinoma gástrico. Los mecanismos patogé-nicos de H. pylori y su relación con los padecimientos gás-tricos no se han definido en forma clara. Sin embargo, actualmente está bien establecido que la ureasa, la citotoxina vacuolizante VacA y los productos de los genes de la isla de patogenicidad (cag PAI) son los principales factores de virulencia de este organismo. Así, los individuos infectados con cepas que expresan dichos factores de virulencia, probablemente manifiesten una marcada inflamación local que podría inducir el desarrollo de úlcera péptica y cáncer gástri-co. La manera como la infección se propaga a nivel mundial sugiere la posibilidad de múltiples vías de transmisión. A consecuencia de la importancia que H. pylori ha adquirido como patógeno humano, los laboratorios del mundo se esfuerzan para desarrollar una vacuna que confiera protección inmunológica de larga duración contra la infección por este microorganismo. El objetivo de esta revisión es presentar los hallazgos más relevantes sobre la biología de H. pylori y su interacción con su huésped humano. El texto completo de este artículo también está disponible en:

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Section: Vaccination Development For Clinical Use and Future Of The Hmentioning

confidence: 66%

Section: Vaccination Development For Clinical Use and Future Of The Hmentioning

confidence: 99%

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

Aguilar¹,

Ayala²,

Fierros-Zarate³

2001

Salud pública Méx

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“…The immune response against H. pylori infection in mice and humans is ineffective in controlling the bacteria and appears to be biased towards a Th1 response (1,11,26,38,39,44). In contrast, the results of several studies in mice suggest that type 2 responses characterized by IL-4 secretion are important in immunity against this pathogen (18,26,27,36,38), but their significance has never been tested under stringent conditions.…”

Section: Several Groups Recently Identified Cd4mentioning

confidence: 76%

Adoptive Transfer of CD4⁺T Cells Specific for Subunit A ofHelicobacter pyloriUrease ReducesH. pyloriStomach Colonization in Mice in the Absence of Interleukin-4 (IL-4)/IL-13 Receptor Signaling

et al. 2001

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Protection in the murine model of Helicobacter pylori infection may be mediated by CD4؉ T cells, but the mechanism remains unclear. To better understand how protection occurs in this model, we generated and characterized H. pylori urease-specific CD4 ؉ T cells from BALB/c mice immunized with Salmonella enterica serovar Typhimurium expressing H. pylori urease (subunits A and B). The CD4 ؉ T cells were found to be specific for subunit A (UreA). Upon antigen-specific stimulation, expression of interleukin 4 (IL-4), IL-10, gamma interferon (IFN-␥), and tumor necrosis factor alpha was induced. Immunocytochemical analysis showed that the majority of cells produced IFN-␥ and IL-10. Adoptive transfer of the UreA-specific CD4 ؉ T cells into naive syngeneic recipients led to a threefold reduction in the number of bacteria in the recipient group when compared to that in the nonrecipient group. Stomach colonization was also reduced significantly after transfer of these cells into patently infected mice. Adoptive transfer of UreA-specific CD4 ؉ T cells into IL-4 receptor ␣ chain-deficient BALB/c mice indicated that IL-4 and IL-13 were not critical in the control of bacterial load. In addition, synthetic peptides were used to identify three functional T-cell epitopes present in subunit A which were recognized by the UreA-specific T cells. Analysis of H. pylori-specific cellular immune responses in recipient challenged and nonrecipient infected mice indicated a strong local restriction of the response in infected animals. The implications of these findings for the mechanism of protection and the development of peptide-based vaccination are discussed.

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“…The initial migration of inflammatory cells into the gastric mucosa and their activation are believed to depend on the production of proinflammatory cytokines (2,8,17,(30)(31)(32). The inflammatory products from the polymorphonuclear cells (PMNs) and mononuclear cells (MNCs) are also thought to damage the epithelial layer and play a role in disease pathogenesis.…”

mentioning

confidence: 99%

Natural History of Gastric Mucosal Cytokine Expression inHelicobacter pyloriGastritis in Mongolian Gerbils

Yamaoka

Yamauchi

Ota³

et al. 2005

Infect Immun

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Data regarding the chronological changes in gastric mucosal cytokines in the different phases of Helicobacter pylori infection are unavailable. We examined Mongolian gerbils for up to 52 weeks after H. pylori (ATCC 43504) inoculation. Levels of mRNAs of mucosal cytokines (interleukin-1␤ [IL-1␤], gamma interferon [IFN-␥], IL-4, IL-6, and IL-10) were assessed using real-time reverse transcription-PCR. Starting 26 weeks after H. pylori inoculation, two clinicohistologic patterns appeared: gastric ulcers in 32% and hyperplastic polyps in 68% of gerbils. High levels of mucosal IL-1␤ mRNA were observed early in the infection, reaching maximum at 4 weeks and then rapidly declining. Mucosal IFN-␥ mRNA also reached maximal levels at 4 weeks but remained high thereafter. Both IL-1␤ and IFN-␥ mRNA levels were consistently higher in the pyloric mucosa than in the fundic mucosa. In contrast, IL-4, IL-6, and IL-10 mRNA levels peaked at 8 to 26 weeks and levels were similar in the pyloric mucosa and the fundic mucosa. IFN-␥ mRNA levels were significantly higher in gerbils with ulcers than in those with hyperplastic polyps (median IFN-␥/glyceraldehyde-3-phosphate dehydrogenase ratio ؋ 100,000 ‫؍‬ 650 versus 338, respectively [antrum], and 172 versus 40, respectively [corpus]) (P < 0.05). We propose that the different outcomes (e.g., ulcers or hyperplastic polyps) might relate to imbalances among cytokines.Helicobacter pylori infection of the gastric mucosa is characterized by the infiltration of neutrophils, lymphocytes, monocytes, and plasma cells. The initial migration of inflammatory cells into the gastric mucosa and their activation are believed to depend on the production of proinflammatory cytokines (2,8,17,(30)(31)(32). The inflammatory products from the polymorphonuclear cells (PMNs) and mononuclear cells (MNCs) are also thought to damage the epithelial layer and play a role in disease pathogenesis. T-helper (Th) cells are also found in the gastric lamina propria in H. pylori infection. The cytokine response in the gastric mucosa of patients chronically infected with H. pylori is thought to be predominantly of the Th1 type (1,2,5,7,8,10,11,15,17,18,22,(24)(25)(26). This determination was based in part on the presence of increased numbers of gamma interferon (IFN-␥)-secreting T cells in H. pylori-infected gastric mucosa compared to normal mucosa (2,5,11,15,17,25). H. pylori-infected IFN-␥-knockout mice developed minimal pathological changes (1,22,24), consistent with the response to H. pylori infection being primarily a Th1-type response.However, the relative contribution of the different cytokines during the course of the infection is still unknown. It is generally impossible to characterize the natural history of the immune response to H. pylori in humans, but such studies are possible using animal models. Rodents are excellent model animals in that they can be infected with H. pylori strains that consistently produce severe gastritis. In particular, Mongolian gerbils (Meriones unguiculatus) infected with selected stra...

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Naturally acquired human immune responses againstHelicobacter pylori and implications for vaccine development

Cited by 55 publications

References 126 publications

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

Adoptive Transfer of CD4⁺T Cells Specific for Subunit A ofHelicobacter pyloriUrease ReducesH. pyloriStomach Colonization in Mice in the Absence of Interleukin-4 (IL-4)/IL-13 Receptor Signaling

Natural History of Gastric Mucosal Cytokine Expression inHelicobacter pyloriGastritis in Mongolian Gerbils

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Naturally acquired human immune responses againstHelicobacter pylori and implications for vaccine development

Cited by 55 publications

References 126 publications

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

Helicobacter pylori: recent advances in the study of its pathogenicity and prevention

Adoptive Transfer of CD4+T Cells Specific for Subunit A ofHelicobacter pyloriUrease ReducesH. pyloriStomach Colonization in Mice in the Absence of Interleukin-4 (IL-4)/IL-13 Receptor Signaling

Natural History of Gastric Mucosal Cytokine Expression inHelicobacter pyloriGastritis in Mongolian Gerbils

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Adoptive Transfer of CD4⁺T Cells Specific for Subunit A ofHelicobacter pyloriUrease ReducesH. pyloriStomach Colonization in Mice in the Absence of Interleukin-4 (IL-4)/IL-13 Receptor Signaling