Murine CD4 T-cell response to Helicobacter infection: TH1 cells enhance gastritis and TH2 cells reduce bacterial load

Mohammadi, Marjan; Nedrud, John G.; Redline, R.; Lycke, Nils; Czinn, Steven J.

doi:10.1016/s0016-5085(97)70004-0

Cited by 267 publications

(211 citation statements)

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“…CD4 1 T cells are required for protection in animal models of vaccination, and adoptive transfer of these cells leads to reductions in colonisation in naïve recipients [14,15]. This observation has also been supported by data from a recent trial of a recombinant attenuated Salmonella enterica serovar Typhi (S. Typhi)-based H. pylori vaccine in human volunteers.…”

Section: Introductionmentioning

confidence: 76%

“…On the other, while a recent trial of a combined CagA/ NapA/alum formulation delivered via the intramuscular route was reported to induce strong antibody T-cell responses after four doses [10], most studies investigating mucosal vaccination approaches with live or protein-adjuvanted vaccines have been reported to induce weak, systemic immune responses in humans, as reflected by measurable antibody and T-cell responses [6,[11][12][13]. A better understanding of the immunological mechanisms underlying vaccination is therefore essential to aid development of an effective vaccine for humans.CD4 1 T cells are required for protection in animal models of vaccination, and adoptive transfer of these cells leads to reductions in colonisation in naïve recipients [14,15]. This observation has also been supported by data from a recent trial of a recombinant attenuated Salmonella enterica serovar Typhi (S. Typhi)-based H. pylori vaccine in human volunteers.…”

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confidence: 76%

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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: Introductionmentioning

confidence: 76%

mentioning

confidence: 76%

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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“…On the other hand, IL-4 does not seem to be critical in H. pylori infection (1,5,20), whereas it plays an important role in H. felis infection of mice (22), and Smythies et al (29) found stronger gastric inflammation in IL-4-deficient mice. Chen et al reported significantly reduced colonization of the gastric mucosa in IL-10-deficient mice so that IL-10 seemed to be an inhibitor of the protective immune response to H. pylori infection (6).…”

Section: Discussionmentioning

confidence: 99%

Role of Tumor Necrosis Factor‐Alpha and Interferon‐Gamma in Helicobacter pylori Infection

Yamamoto

Kita

Ohno

et al. 2004

Microbiology and Immunology

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Immune responses to Helicobacter pylori infection play important roles in gastroduodenal diseases. The contributions of tumor necrosis factor‐α (TNF‐α) and interferon‐7 (IFN‐γ) to the induction of gastric inflammation and to the protection from H. pylori infection were investigated using TNF‐α gene‐knockout (TNF‐α−/−) mice and IFN‐γ gene‐knockout (IFN‐γ−/−) mice. We first examined the colonizing ability of H. pylori strain CPY2052 in the stomach of C57BL/6 wild‐type and knockout mice. The number of H. pylori colonized in the stomach of IFN‐γ−/− and TNF‐α−/− mice was higher than that of wild‐type mice. These findings suggest that TNF‐α and IFN‐γ may play a protective role in H pylori infection. Furthermore, we examined the contribution of TNF‐α and IFN‐γ to gastric inflammation. The CPY2052‐infected TNF‐α−/− mice showed a moderate infiltration of mononuclear cells in the lamina propria and erosions in the gastric epithelium as did wild‐type mice, whereas the CPY2052‐infected IFN‐γ−/− mice showed no inflammatory findings even 6 months after infection. These results demonstrate that IFN‐γ may play an important role in gastric inflammation induced by H. pylori infection, whereas TNF‐α may not participate in the development of inflammatory response.

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“…Similar results were obtained by Smythies et al (9) in H. pylori-infected IL-4 -/-mice. Conversely, Mohammadi et al (33) showed that, in H. felis infection, the number of bacteria is greater in IL-4 -/-than in WT C57BL/6 mice. In addition, Zavros et al (34) showed that treatment with IL-4 reduced the H. felis load in a Th1 mouse model of Helicobacter infection.…”

Section: Microbiological Studymentioning

confidence: 95%

<a name="home"></a>The role of IFN-gamma and IL-4 in gastric mucosa inflammation associated with Helicobacter heilmannii type 1 infection

Cinque

Rocha

Correa-Oliveira

et al. 2006

Braz J Med Biol Res

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Although Helicobacter heilmannii infection is less common than H. pylori infection in humans, it is considered to be of medical importance because of its association with gastritis, gastric ulcer, carcinoma, and mucosa-associated lymphoid tissue lymphoma of the stomach. However, there have been no studies evaluating the role of the Th cell response in H. heilmannii gastric infection. We evaluated the participation of pro-inflammatory and anti-inflammatory cytokines, IFN-γ and IL-4, in H. heilmannii gastric infection in genetically IFN-γ-or IL-4-deficient mice. The serum IFN-γ and IL-4 concentrations were determined by ELISA. The gastric polymorphonuclear infiltrate was higher (P = 0.007) in H. heilmannii-positive than in H. heilmanniinegative wild-type (WT) C57BL/6 mice, whereas no significant inflammation was demonstrable in the stomach of H. heilmannii-positive IFN-γ -/-C57BL/6 mice. The degree of gastric inflammatory cells, especially in oxyntic mucosa, was also higher (P = 0.007) in infected IL-4 -/-than in WT BALB/c mice. Serum IFN-γ levels were significantly higher in IL-4 -/-than in WT BALB/c mice, independently of H. heilmannii-positive or -negative status. Although no difference in serum IFN-γ levels was seen between H. heilmannii-positive (11.3 ± 3.07 pg/mL, mean ± SD) and -negative (11.07 ± 3.5 pg/mL) WT BALB/c mice, in the group of IL-4 -/-animals, the serum concentration of IFN-γ was significantly higher in the infected ones (38.16 ± 10.5 pg/ mL, P = 0.04). In contrast, serum IL-4 levels were significantly decreased in H. heilmannii-positive (N = 10) WT BALB/c animals compared to the negative (N = 10) animals. In conclusion, H. heilmannii infection induces a predominantly Th1 immune response, with IFN-γ playing a central role in gastric inflammation.

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Murine CD4 T-cell response to Helicobacter infection: TH1 cells enhance gastritis and TH2 cells reduce bacterial load

Cited by 267 publications

References 3 publications

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

Role of Tumor Necrosis Factor‐Alpha and Interferon‐Gamma in Helicobacter pylori Infection

<a name="home"></a>The role of IFN-gamma and IL-4 in gastric mucosa inflammation associated with Helicobacter heilmannii type 1 infection

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