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Immunodominant epitope-specific Th1 but not Th17 responses mediate protection against Helicobacter pylori infection following UreB vaccination of BALB/c mice.

Li B, Chen L, Sun H, Yang W, Hu J, He Y, Wei S, Zhao Z, Zhang J, Li H, Zou Q, Wu C - Sci Rep (2015)

Bottom Line: Previous studies have confirmed the effectiveness of rUreB subunit vaccines in generating CD4(+) T-cell-mediated protection, but less is known regarding the roles of different subtypes of T-cell immunity, such as Th1, Th2 and Th17, particularly the immunodominant epitopes inducing specific CD4(+) T-cell responses, in vaccine-mediated protection.Our results demonstrated that two novel epitopes can simultaneously induce Th1 and Th17 immune responses; however, only the epitope vaccine-induced CD4(+) T-cells secreting IFN-γ mediated the protection against H. pylori; cells secreting IL-17A did not.Taken together, our results suggest that two novel immunodominant epitopes can induce Th1 and Th17 immune responses, but only the induced Th1 lymphocytes mediate protection against H. pylori.

View Article: PubMed Central - PubMed

Affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.

ABSTRACT
Helicobacter pylori (H. pylori) infects more than half of the world's population, causing chronic gastritis, peptic ulcers and gastric cancer. Urease B subunit (UreB), a conserved protein of H. pylori, is capable of inducing specific CD4(+) T-cell responses and provides protection against this infection. Previous studies have confirmed the effectiveness of rUreB subunit vaccines in generating CD4(+) T-cell-mediated protection, but less is known regarding the roles of different subtypes of T-cell immunity, such as Th1, Th2 and Th17, particularly the immunodominant epitopes inducing specific CD4(+) T-cell responses, in vaccine-mediated protection. In this study, we demonstrated that the vaccination of BALB/c mice with rUreB resulted in significant antigen-specific Th1 and Th17 immune responses. Importantly, two novel Th epitopes, UreB317-329 and UreB409-421, which are recognized by a major population of CD4(+) T cells, were identified in immunized mice. Our results demonstrated that two novel epitopes can simultaneously induce Th1 and Th17 immune responses; however, only the epitope vaccine-induced CD4(+) T-cells secreting IFN-γ mediated the protection against H. pylori; cells secreting IL-17A did not. Taken together, our results suggest that two novel immunodominant epitopes can induce Th1 and Th17 immune responses, but only the induced Th1 lymphocytes mediate protection against H. pylori.

No MeSH data available.


Related in: MedlinePlus

Effect of two novel immunodominant epitopes against H. pylori infection.(a) H. pylori colonization in the stomachs of mice immunized with peptides was determined using real-time quantitative PCR. (b) The number of gastric mucosal CD4+ T lymphocytes was analyzed using flow cytometry (left). Gastric mucosal CD4+ T cells expressing α4β7 homing receptors were quantified (middle). Gastric mucosal CD4+ T cells expressing L-selectin chemokine receptors were determined (right). (c) Gastric inflammation scores of mice immunized with peptides were identified 4 weeks after infection and representative gastric histopathology of immunized mice and PBS controls are shown (H&E staining, original magnification × 200). (d) The epitope-specific CD4+ T-cell responses, including Th1, Th17 and Th2, of mice immunized with UreB317–329 peptide were analyzed. (e) The epitope-specific CD4+ T-cell responses, including Th1, Th17 and Th2, of mice immunized with UreB409–421 peptide were determined. All data were repeated more than three times. The data are expressed as the mean ± S.D (n = 10). **P < 0.01, ***P < 0.001.
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f5: Effect of two novel immunodominant epitopes against H. pylori infection.(a) H. pylori colonization in the stomachs of mice immunized with peptides was determined using real-time quantitative PCR. (b) The number of gastric mucosal CD4+ T lymphocytes was analyzed using flow cytometry (left). Gastric mucosal CD4+ T cells expressing α4β7 homing receptors were quantified (middle). Gastric mucosal CD4+ T cells expressing L-selectin chemokine receptors were determined (right). (c) Gastric inflammation scores of mice immunized with peptides were identified 4 weeks after infection and representative gastric histopathology of immunized mice and PBS controls are shown (H&E staining, original magnification × 200). (d) The epitope-specific CD4+ T-cell responses, including Th1, Th17 and Th2, of mice immunized with UreB317–329 peptide were analyzed. (e) The epitope-specific CD4+ T-cell responses, including Th1, Th17 and Th2, of mice immunized with UreB409–421 peptide were determined. All data were repeated more than three times. The data are expressed as the mean ± S.D (n = 10). **P < 0.01, ***P < 0.001.

Mentions: To investigate the protective effect of two immunodominant epitopes against H. pylori infection, mice were immunized with either UreB317–329 or UreB409–421 and challenged with H. pylori. Real-time quantitative PCR was used to measure H. pylori colonization in the gastric mucosal four weeks post-challenge. As shown in Fig. 5a, the levels of H. pylori colonization in the peptide-immunized groups were considerably lower than those in PBS controls. Robust protection was observed in mice immunized with UreB317–329 and UreB409–421 (Fig. 5a), and immunization with UreB317–329 demonstrated a more significant protective effect than UreB409–421.


Immunodominant epitope-specific Th1 but not Th17 responses mediate protection against Helicobacter pylori infection following UreB vaccination of BALB/c mice.

Li B, Chen L, Sun H, Yang W, Hu J, He Y, Wei S, Zhao Z, Zhang J, Li H, Zou Q, Wu C - Sci Rep (2015)

Effect of two novel immunodominant epitopes against H. pylori infection.(a) H. pylori colonization in the stomachs of mice immunized with peptides was determined using real-time quantitative PCR. (b) The number of gastric mucosal CD4+ T lymphocytes was analyzed using flow cytometry (left). Gastric mucosal CD4+ T cells expressing α4β7 homing receptors were quantified (middle). Gastric mucosal CD4+ T cells expressing L-selectin chemokine receptors were determined (right). (c) Gastric inflammation scores of mice immunized with peptides were identified 4 weeks after infection and representative gastric histopathology of immunized mice and PBS controls are shown (H&E staining, original magnification × 200). (d) The epitope-specific CD4+ T-cell responses, including Th1, Th17 and Th2, of mice immunized with UreB317–329 peptide were analyzed. (e) The epitope-specific CD4+ T-cell responses, including Th1, Th17 and Th2, of mice immunized with UreB409–421 peptide were determined. All data were repeated more than three times. The data are expressed as the mean ± S.D (n = 10). **P < 0.01, ***P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4593181&req=5

f5: Effect of two novel immunodominant epitopes against H. pylori infection.(a) H. pylori colonization in the stomachs of mice immunized with peptides was determined using real-time quantitative PCR. (b) The number of gastric mucosal CD4+ T lymphocytes was analyzed using flow cytometry (left). Gastric mucosal CD4+ T cells expressing α4β7 homing receptors were quantified (middle). Gastric mucosal CD4+ T cells expressing L-selectin chemokine receptors were determined (right). (c) Gastric inflammation scores of mice immunized with peptides were identified 4 weeks after infection and representative gastric histopathology of immunized mice and PBS controls are shown (H&E staining, original magnification × 200). (d) The epitope-specific CD4+ T-cell responses, including Th1, Th17 and Th2, of mice immunized with UreB317–329 peptide were analyzed. (e) The epitope-specific CD4+ T-cell responses, including Th1, Th17 and Th2, of mice immunized with UreB409–421 peptide were determined. All data were repeated more than three times. The data are expressed as the mean ± S.D (n = 10). **P < 0.01, ***P < 0.001.
Mentions: To investigate the protective effect of two immunodominant epitopes against H. pylori infection, mice were immunized with either UreB317–329 or UreB409–421 and challenged with H. pylori. Real-time quantitative PCR was used to measure H. pylori colonization in the gastric mucosal four weeks post-challenge. As shown in Fig. 5a, the levels of H. pylori colonization in the peptide-immunized groups were considerably lower than those in PBS controls. Robust protection was observed in mice immunized with UreB317–329 and UreB409–421 (Fig. 5a), and immunization with UreB317–329 demonstrated a more significant protective effect than UreB409–421.

Bottom Line: Previous studies have confirmed the effectiveness of rUreB subunit vaccines in generating CD4(+) T-cell-mediated protection, but less is known regarding the roles of different subtypes of T-cell immunity, such as Th1, Th2 and Th17, particularly the immunodominant epitopes inducing specific CD4(+) T-cell responses, in vaccine-mediated protection.Our results demonstrated that two novel epitopes can simultaneously induce Th1 and Th17 immune responses; however, only the epitope vaccine-induced CD4(+) T-cells secreting IFN-γ mediated the protection against H. pylori; cells secreting IL-17A did not.Taken together, our results suggest that two novel immunodominant epitopes can induce Th1 and Th17 immune responses, but only the induced Th1 lymphocytes mediate protection against H. pylori.

View Article: PubMed Central - PubMed

Affiliation: National Engineering Research Center of Immunological Products, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy, Third Military Medical University, Chongqing 400038, P.R. China.

ABSTRACT
Helicobacter pylori (H. pylori) infects more than half of the world's population, causing chronic gastritis, peptic ulcers and gastric cancer. Urease B subunit (UreB), a conserved protein of H. pylori, is capable of inducing specific CD4(+) T-cell responses and provides protection against this infection. Previous studies have confirmed the effectiveness of rUreB subunit vaccines in generating CD4(+) T-cell-mediated protection, but less is known regarding the roles of different subtypes of T-cell immunity, such as Th1, Th2 and Th17, particularly the immunodominant epitopes inducing specific CD4(+) T-cell responses, in vaccine-mediated protection. In this study, we demonstrated that the vaccination of BALB/c mice with rUreB resulted in significant antigen-specific Th1 and Th17 immune responses. Importantly, two novel Th epitopes, UreB317-329 and UreB409-421, which are recognized by a major population of CD4(+) T cells, were identified in immunized mice. Our results demonstrated that two novel epitopes can simultaneously induce Th1 and Th17 immune responses; however, only the epitope vaccine-induced CD4(+) T-cells secreting IFN-γ mediated the protection against H. pylori; cells secreting IL-17A did not. Taken together, our results suggest that two novel immunodominant epitopes can induce Th1 and Th17 immune responses, but only the induced Th1 lymphocytes mediate protection against H. pylori.

No MeSH data available.


Related in: MedlinePlus