Characterization of the<i>Helicobacter pylori</i>Cysteine-Rich Protein A as a T-Helper Cell Type 1 Polarizing Agent

Deml, Ludwig; Aigner, Michael; Decker, Jochen; Eckhardt, Alexander; Schütz, Christian; Mittl, Peer R. E.; Barabas, Sascha; Denk, Stefanie; Knoll, Gertrud; Lehn, Norbert; Schneider-Brachert, Wulf

doi:10.1128/iai.73.8.4732-4742.2005

Cited by 42 publications

(40 citation statements)

References 57 publications

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“…For example, positive selection was more evident in the East Asian and The Gambian hp0160 lineages (x ¼ 2.26 and 2.32, respectively), than in South African and European lineages (x ¼ 0.29 and 0.001, respectively). Similar lineagespecific positive selection was also seen in phylogenies of hp1117 and of hp0211; Hp0211 (HcpA) protein induces a cytokine IL12-mediated pro-inflammatory response [30]. Although SSMs suggested heterogeneous selective pressures and rapid evolution of certain codons in hp0235, LSMs indicated that x did not vary significantly among the lineages studied (Table S11); a sampling of additional populations, however, might identify hp0235 lineages that had evolved more rapidly.…”

Section: Most Slr Genes Evolve Rapidly Often In Discrete H Pylori Lmentioning

confidence: 88%

“…High antibody titres against four SLR proteins [Hp0211 (HcpA), Hp0235 (HcpE), Hp0336 (HcpB), and Hp1098 (HcpC)] were found in H. pylori-infected people [28], indicating in vivo expression and immune recognition. Furthermore, recombinant HcpA elicited IL12-dependent IFN-c secretion in a naïve mouse splenocyte model [30], and HP1117 elicited protective antibodies during mouse infection [31]. Only one or two slr homologs are found in members of the closely related Campylobacter and Wolinella genera, whereas strains of H. acinonychis (from big cats) and of the nongastric mouse pathogen H. hepaticus (implicated in liver cancer) contain seven and six slr homologs, respectively ( Figure 1A).…”

Section: Introductionmentioning

confidence: 99%

“…Five of the nine members of this ''SLR'' (for Sel1-like repeat) protein family are rich in cysteine residues and had been designated as ''Helicobacter cysteine rich proteins'' (Hcp) [27,28]; The ahelices of each SLR repeat are bridged by a disulfide bond, which is a unique feature of Hcps [26]. Although the in vivo function of H. pylori SLR proteins is not known, some Hcps bind b-lactam compounds [27,29], which suggests possible interactions with immunomodulatory peptidoglycan fragments, that could affect the innate immune response [30]. High antibody titres against four SLR proteins [Hp0211 (HcpA), Hp0235 (HcpE), Hp0336 (HcpB), and Hp1098 (HcpC)] were found in H. pylori-infected people [28], indicating in vivo expression and immune recognition.…”

Section: Introductionmentioning

confidence: 99%

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Helicobacter pylori Evolution: Lineage-Specific Adaptations in Homologs of Eukaryotic Sel1-Like Genes

et al. 2005

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Geographic partitioning is postulated to foster divergence of Helicobacter pylori populations as an adaptive response to local differences in predominant host physiology. H. pylori's ability to establish persistent infection despite host inflammatory responses likely involves active management of host defenses using bacterial proteins that may themselves be targets for adaptive evolution. Sequenced H. pylori genomes encode a family of eight or nine secreted proteins containing repeat motifs that are characteristic of the eukaryotic Sel1 regulatory protein, whereas the related Campylobacter and Wolinella genomes each contain only one or two such ''Sel1-like repeat'' (SLR) genes (''slr genes''). Signatures of positive selection (ratio of nonsynonymous to synonymous mutations, d N /d S ¼ x . 1) were evident in the evolutionary history of H. pylori slr gene family expansion. Sequence analysis of six of these slr genes (hp0160, hp0211, hp0235, hp0519, hp0628, and hp1117) from representative East Asian, European, and African H. pylori strains revealed that all but hp0628 had undergone positive selection, with different amino acids often selected in different regions. Most striking was a divergence of Japanese and Korean alleles of hp0519, with Japanese alleles having undergone particularly strong positive selection (x J . 25), whereas alleles of other genes from these populations were intermingled. Homology-based structural modeling localized most residues under positive selection to SLR protein surfaces. Rapid evolution of certain slr genes in specific H. pylori lineages suggests a model of adaptive change driven by selection for fine-tuning of host responses, and facilitated by geographic isolation. Characterization of such local adaptations should help elucidate how H. pylori manages persistent infection, and potentially lead to interventions tailored to diverse human populations.

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Section: Most Slr Genes Evolve Rapidly Often In Discrete H Pylori Lmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Helicobacter pylori Evolution: Lineage-Specific Adaptations in Homologs of Eukaryotic Sel1-Like Genes

et al. 2005

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“…Furthermore, it has been shown that IL-6 levels are correlated with the severity of atrophic gastritis in H. pylori infections (32)(33)(34). Also, IL-12 response with IFN-γ plays an important role in the H. pylori pathogenesis and development of ulcers (35)(36)(37). Furthermore, IL-10, acting as an anti-inflammatory cytokine, suppresses proinflammatory cytokines, causes a persistent H. pylori infection, and prevents immunopathologies with its inhibitory effects on IL-12-driven Th1 response (25,38).…”

Section: Discussionmentioning

confidence: 99%

The cytokine response in THP-1 (monocyte) and HL-60 (neutrophil-differentiated) cells infected with different genotypes of Helicobacter pylori strains

Caliskan

Sayi-Yazgan²,

Tokman³

et al. 2015

Turk J Gastroenterol

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Background/Aims: Helicobacter pylori (H. pylori) is a microaerophilic bacterium related with peptic ulcer and gastric cancer. Its virulence factors include cytotoxin-associated gene A (CagA) and vacuolating cytotoxin gene A (VacA) proteins. Cytokine release inducted by H. pylori colonization has an important role in pathogenesis of H. pylori. The severity of gastric pathologies depends on the H. pylori genotypes found in different geographical regions. We aimed to determine the relationship between different H. pylori genotypes and their effects on the cytokine release levels. Materials and Methods: ureC, cagA, vacAs1/s2, vacAm1/m2, and blood group antigen-binding adhesion protein A2 (babA2) virulence related genes were investigated in 21 H. pylori strains. Genotyping of 21 strains were made due to the presence of cagA, vacAs1/s2, vacAm1/m2, and babA2 genes. The H. pylori strains were cultured together with THP-1 and neutrophil-differentiated Human promyelocytic leukemia cells (HL-60) cells. The levels of cytokines interleukin (IL)-1β, IL-6, IL-8, IL-12, tumor necrosis factor-alpha (TNF-α), and IL-10 in these cells were measured after co-culturing with H. pylori strains. Results: The following five different genotypes were detected: Genotype1: cagA and vacAs1m2; Genotype2: cagA and vacAs1m1; Genotype3: cagA, vacAs1m2, and babA2; Genotype4: vacAs2m2; and Genotype5: cagA and vacAs2m2. All these genotypes significantly induced the levels of IL-1β, IL-6, IL-8, IL 10, and TNF-α in THP-1 cells. Genotype 5 caused higher amounts of IL-1β, IL-6, TNF-α, and IL-10, whereas genotype 1 induced the highest levels of IL-8. In neutrophil-differentiated HL-60 cells, genotype 4 increased IL-6 levels and genotype 3 and 4 elevated IL-8 levels significantly. Conclusion: These results suggested that cytokine response of the host varies depending on the specific immune response of the host against different H. pylori strains.

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“…Mild and moderate cases, n (%) Controls, n (%) OR (95% CI) (37,38), and UreA (39,40) have been shown to play immune protective roles in in vitro experiments; Cagy and CagM were found to be essential for translocation of CagA into gastric epithelial cells (41); Omp was identified as a secreted protein and was suggested to contribute to gastric inflammation and epithelial damage (42); and HcpC (a surface protein) was suggested to participate in proinflammatory response like other helicobacter cysteine-rich proteins (43,44). Eight of these markers have been shown to be associated with gastric diseases (gastric cancer and peptic ulcer) in clinical settings: Cad, CagM, HP0305, HpaA, HyuA, GroEL, NapA, and UreA (14,16,45).…”

Section: Serostatusmentioning

confidence: 99%

Association between Chronic Atrophic Gastritis and Serum Antibodies to 15 Helicobacter pylori Proteins Measured by Multiplex Serology

Gao¹,

Weck²,

Michel

et al. 2009

Cancer Research

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Infection with Helicobacter pylori is a major risk factor for chronic atrophic gastritis (CAG), a precursor lesion of intestinal gastric cancer. The pathogenicity of the bacterium is thought to play an important role in determining the extent and severity of clinical outcome. We aimed to assess the associations between CAG and the serostatus of antibodies to 15 H. pylori proteins. The analyses were based on 534 cases with serologically defined CAG and 1,068 age-matched and sex-matched controls participating in a population-based study conducted in Saarland, Germany among 9,953 men and women ages 50 to 74 years. A newly developed H. pylori multiplex serology method was used to detect antibodies specific to 15 H. pylori antigens. Significant associations were observed between seropositivity for all 15 specific antibodies and the presence of CAG. Exclusion of severe cases, who might have lost the infection in the course of CAG progression, substantially increased the observed associations. In H. pylori-seropositive subjects, cytotoxin-associated gene A (CagA), vacuolating toxin (VacA), helicobacter cysteine-rich protein C (HcpC), and the chaperonin GroEL were identified as independent virulence factors for CAG with adjusted odds ratios (95% confidence interval) of 3.52 (2.01-6.10), 3.19 (1.44-7.05), 4.03 (1.53-10.65), and 2.65 (1.06-6.62), respectively; the simultaneous presence of all four independent virulence factors was associated with an 18-fold risk of CAG. In conclusion, HcpC and GroEL were identified as new independent virulence factors, and in combination with the established virulence factors, CagA and VacA, were strongly associated with CAG.

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Characterization of theHelicobacter pyloriCysteine-Rich Protein A as a T-Helper Cell Type 1 Polarizing Agent

Cited by 42 publications

References 57 publications

Helicobacter pylori Evolution: Lineage-Specific Adaptations in Homologs of Eukaryotic Sel1-Like Genes

Helicobacter pylori Evolution: Lineage-Specific Adaptations in Homologs of Eukaryotic Sel1-Like Genes

The cytokine response in THP-1 (monocyte) and HL-60 (neutrophil-differentiated) cells infected with different genotypes of Helicobacter pylori strains

Association between Chronic Atrophic Gastritis and Serum Antibodies to 15 Helicobacter pylori Proteins Measured by Multiplex Serology

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