<i>Helicobacter pylori</i>Infection in Immunized Mice Lacking Major Histocompatibility Complex Class I and Class II Functions

Pappo, Jacques; Torrey, D.; Castriotta, Lillian; Savinainen, Anneli; Kabok, Zita; Ibraghimov, Alexander

doi:10.1128/iai.67.1.337-341.1999

Cited by 148 publications

(43 citation statements)

References 30 publications

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“…The immune responses to H. pylori that occur in experimentally infected animals and in naturally infected humans are typically ineffective in eradicating H. pylori. However, studies in animal models indicate that H. pylori infection can be prevented by prophylactic immunization (Ermak et al, 1998;Pappo et al, 1999;Akhiani et al, 2002Akhiani et al, , 2004Garhart et al, 2003), and established infections can potentially be eradicated via therapeutic immunization (Vyas & Sihorkar, 1999;Sutton et al, 2000;Li et al, 2004). An important goal for future studies will be to understand more clearly the immunologic determinants of protective immunity against H. pylori, and to determine why immune responses to H. pylori fail to eradicate the infection in most infected humans.…”

Section: Discussionmentioning

confidence: 99%

Host response toHelicobacter pyloriinfection before initiation of the adaptive immune response

Algood

Gallo-Romero

Wilson

et al. 2007

FEMS Immunology &Amp; Medical Microbiology

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Helicobacter pylori persistently colonizes the human stomach. In this study, immune responses to H. pylori that occur in the early stages of infection were investigated. Within the first 2 days after orogastric infection of mice with H. pylori, there was a transient infiltration of macrophages and neutrophils into the glandular stomach. By day 10 postinfection, the numbers of macrophages and neutrophils decreased to baseline levels. By 3 weeks postinfection, an adaptive immune response was detected, marked by gastric infiltration of T lymphocytes, macrophages, and neutrophils, as well as increased numbers of H. pylori-specific T cells, macrophages, and dendritic cells in paragastric lymph nodes. Neutrophil-attracting and macrophage-attracting chemokines were expressed at higher levels in the stomachs of H. pylori-infected mice than in the stomachs of uninfected mice. Increased expression of TNFalpha and IFNgamma (Th1-type inflammatory cytokines) and IL-17 (a Th17-type cytokine) was detected in the stomachs of H. pylori-infected mice, but increased expression of IL-4 (a Th2-type cytokine) was not detected. These data indicate that a transient gastric inflammatory response to H. pylori occurs within the first few days after infection, before the priming of T cells and initiation of an adaptive immune response. It is speculated that inappropriate waning of the innate immune response during early stages of infection may be a factor that contributes to H. pylori persistence.

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Section: Discussionmentioning

confidence: 99%

Host response toHelicobacter pyloriinfection before initiation of the adaptive immune response

Algood

Gallo-Romero

Wilson

et al. 2007

FEMS Immunology &Amp; Medical Microbiology

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“…Numerous studies have attempted to reveal the immunological basis of immunization. As a result of studies using knockout mice, it is now clear that protection is MHCII-dependant (3,4) but that antibodies IFN-γ (5) and IL-4 and IL-13 (6) are not required. Furthermore, it has been reported that CD4+ T cell lines of Th2 (7) or mixed-type (8) could confer protection after transfer to naïve recipients.…”

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confidence: 99%

Transcription profiling analysis of the mechanisms of vaccine‐induced protection against H. pylori

Walduck

Schmitt

Lucas³

et al. 2004

FASEB j.

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Development of a vaccine against H. pylori is regarded as desirable alternative to the current antibiotic therapy regimens. Mice immunized with an attenuated recombinant Salmonella typhimurium expressing H. pylori urease subunits A&B have dramatically reduced bacterial loads after a single dose. The mechanism(s) of protection against this largely extra-cellular pathogen are not fully understood. The aim of this study was to identify genes that were regulated specifically in response to immunization, in order to gain a broader picture of the immune response in the immunized gastric epithelium. Gene expression in RNA isolated from the gastric mucosa of immunized and infected Balb/c mice was compared with that in infected only mice at 1, 3, and 14 days after challenge with a mouse-adapted strain of H. pylori. We show that infection with H. pylori causes an immediate reaction in vivo, which was clearly divided into acute and chronic phases, and further that the transcriptional response in the H. pylori infected and immunized gastric mucosa is unique. Analysis of gene expression patterns at day 14 post-infection suggested not only the beginning of a lymphocytic infiltrate, but of an integrated epithelial response characterized by increased expression of genes controlling cell cycle and turnover. This observation was confirmed in independent experiments. The global approach has brought new insights to the effect of immunization on the gastric epithelium and has led us to propose a new multi-factorial model for the mechanisms underlying vaccine-induced protection.

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“…Vaccine-induced protection against Helicobacter infection in mouse models can occur independently of antibodies (Ermak et al, 1998;Blanchard et al, 1999;Sutton et al, 2000), but has an absolute requirement for CD4 1 T helper cells (Ermak et al, 1998;Pappo et al, 1999). This suggests that the ineffectiveness of prophylactic immunization in naïve C57BL/6 mice may be due to either a poor CD4 response to the rHpaA protein, or a poor translation in immunity from the recombinant vaccine antigen to the native form expressed by the bacteria.…”

Section: Discussionmentioning

confidence: 99%

Effectiveness of vaccinationwith recombinant HpaA fromHelicobacter pyloriis influenced by host genetic background

Sutton¹,

Doidge²,

Pinczower³

et al. 2007

FEMS Immunol Med Microbiol

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Several studies have explored the production and immunogenicity of HpaA as a potential protective antigen against Helicobacter pylori but little is known regarding its protective capabilities. We therefore evaluated the protective efficacy of recombinant HpaA (rHpaA) as a candidate vaccine antigen against H. pylori. To explore the impact of genetic diversity, inbred and outbred mice were prophylactically and therapeutically immunized with rHpaA adjuvanted with cholera toxin (CT). Prophylactic immunization induced a reduction in bacterial colonization in BALB/c and QS mice, but was ineffective in C57BL/6 mice, despite induction of antigen‐specific antibodies. By contrast, therapeutic immunization was effective in all three strains of mice. Prophylactic immunization with CT‐adjuvanted rHpaA was more effective when delivered via the nasal route than following intragastric delivery in BALB/c mice. However, HpaA‐mediated protection was inferior to that induced by bacterial lysate. Hence, protective efficacy is inducible with vaccines containing HpaA, most relevantly shown in an outbred population of mice. The effectiveness of protection induced by HpaA antigen was influenced by host genetics and was less effective than lysate. HpaA therefore has potential for the development of effective immunization against H. pylori but this would probably entail the antigen to be one component of a multiantigenic vaccine.

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Helicobacter pyloriInfection in Immunized Mice Lacking Major Histocompatibility Complex Class I and Class II Functions

Cited by 148 publications

References 30 publications

Host response toHelicobacter pyloriinfection before initiation of the adaptive immune response

Host response toHelicobacter pyloriinfection before initiation of the adaptive immune response

Transcription profiling analysis of the mechanisms of vaccine‐induced protection against H. pylori

Effectiveness of vaccinationwith recombinant HpaA fromHelicobacter pyloriis influenced by host genetic background

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