<i>Helicobacter pylori</i>‐Pulsed Dendritic Cells Induce <i>H. pylori</i>‐Specific Immunity in Mice

Zhang, Min; Berndt, Bradford E.; Eaton, Kathryn A.; Rathinavelu, Sivaprakash; Pierzchala, Anna; Kao, John Y.

doi:10.1111/j.1523-5378.2008.00606.x

Cited by 16 publications

(25 citation statements)

References 23 publications

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“…Gastric quantitative PCR analyses revealed an increase in Foxp3 mRNA expression and a decrease in IL-17/Foxp3 mRNA ratio in HP-DC transferred compared with PBS-DC transferred mice (Figure 5 D and E ). No significant difference in H pylori colonization or gastritis was detected (Supplementary Figure 2), possibly due to the concurrent increase in H pylori –specific immunity induced by HP-DCs 17. These data indicate that HP-DC induces a Treg-skewed response.…”

Section: Resultsmentioning

confidence: 75%

“…DCs isolated from H felis infected stomach also showed increased costimulatory molecules 16. We and Otsu et al previously reported H pylori -pulsed DCs were able to augment anti- H pylori immunity, but neither study was able to completely eradicate H pylori 17, 38. In this study, HP-DC induce both H pylori -specific Treg and Th1/Th17 responses in vivo but the net results is a Treg skewed response; this is a possible explanation for the inability of DC vaccine to completely eradicate H pylori .…”

Section: Discussionmentioning

confidence: 78%

“…We and others have demonstrated CD11c + DC recruitment in the lamina propria of mouse stomach in both acute and chronic gastritis after H pylori infection,14–16 implicating a role for these DCs in the mucosal response against H pylori . Moreover, we and others have shown that H pylori –pulsed DCs in vivo induce H pylori –specific adaptive immune responses 17. Our current goals are to examine the influence of H pylori on the induction of Th17/Treg differentiation by DCs and to study the significance of the Th17/Treg balance in determining bacterial density.…”

Section: Introductionmentioning

confidence: 99%

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Helicobacter pylori Immune Escape Is Mediated by Dendritic Cell–Induced Treg Skewing and Th17 Suppression in Mice

et al. 2010

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Background & Aims Helicobacter pylori infection increases gastric Treg response, which may contribute to H pylori immune escape. We hypothesize that H pylori directs Treg skewing by way of dendritic cells and thus inhibits Th17 immunity. Methods Two-photon microscopy was used to locate dendritic cells in gastric lamina propria of mice. The induction of Th17 and Treg responses by bacteria-pulsed murine bone marrow–derived dendritic cells was analyzed by cytokine production and stimulation of T cell proliferation. The effect of VacA, CagA, TGF-β, and IL-10 on Th17/Treg balance was assessed. The in vivo significance of Tregs on the H pylori–specific Th17 response and H pylori density was determined using anti-CD25 neutralizing antibodies to deplete Tregs in mice. Results We showed that mucosal CD11c+ dendritic cells are located near the surface of normal gastric epithelium and their number increased after H pylori infection. Study of the direct interaction of dendritic cells with H pylori revealed a Treg-skewed response. The Treg skewing was independent of H pylori VacA and CagA and dependent on TGF-β and IL-10. In vivo Treg skewing by adoptive transfer of H pylori–pulsed DCs reduces the ratio of gastric IL-17/Foxp3 mRNA expressions. The depletion of CD25+ Tregs results in early reduction of H pylori density, which is correlated with enhanced peripheral H pylori–specific Th17, but not Th1, response. Conclusions Overall, our study indicates that H pylori alters the DC-polarized Th17/Treg balance towards a Treg-biased response, which suppresses the effective induction of H pylori–specific Th17 immunity.

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Section: Resultsmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 78%

Section: Introductionmentioning

confidence: 99%

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Helicobacter pylori Immune Escape Is Mediated by Dendritic Cell–Induced Treg Skewing and Th17 Suppression in Mice

et al. 2010

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“…Specifically, cells were first treated with low dose E. coli LPS, allowed to rest overnight, and then stimulated with H. pylori sonicate. H. pylori sonicate was used due to its distinct immunomodulatory capabilities, and to provide contrasting H. pylori LPS stimulation to the initial tolerizing stimulus of E. coli LPS [31–35]. Despite exposure to different components, BM-DC tolerance was maintained when assayed for TNF-α and IL-10.…”

Section: Resultsmentioning

confidence: 99%

IRAK-M modulates expression of IL-10 and cell surface markers CD80 and MHC II after bacterial re-stimulation of tolerized dendritic cells

et al. 2012

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“…The importance of Th1 immunity against H. pylori is well established [30-32]. Thus, the ability of H.…”

Section: Discussionmentioning

confidence: 99%

TLR2 Mediates Helicobacter pylori–Induced Tolerogenic Immune Response in Mice

et al. 2013

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We have shown that Helicobacter pylori induces tolerogenic programming of dendritic cells and inhibits the host immune response. Toll-like receptors (TLRs) represent a class of transmembrane pattern recognition receptors essential for microbial recognition and control of the innate immune response. In this study, we examined the role of TLRs in mediating H. pylori tolerogenic programming of dendritic cells and their impact on anti–H. pylori immunity using C57BL/6 wild-type and TLR2-knockout (TLR2KO) mice. We analyzed the response of TLR2KO bone marrow-derived dendritic cells (BMDCs) to H. pylori SS1 stimulation and the outcome of chronic H. pylori infection in TLR2KO mice. We showed that H. pylori–stimulated BMDCs upregulated the expression of TLR2, but not TLR4, TLR5, or TLR9. H. pylori-stimulated BMDCs from TLRKO mice induced lower Treg and Th17 responses, but a higher IFN-γ response compared to H. pylori-stimulated BMDCs from wild-type mice. In vivo analyses following an H. pylori infection of 2 months duration showed a lower degree of gastric H. pylori colonization in TLR2KO mice and more severe gastric immunopathology compared to WT mice. The gastric mucosa of the infected TLR2KO mice showed a lower mRNA expression of Foxp3, IL-10, and IL-17A, but higher expression of IFN-γ compared to the gastric mRNA expression in infected wild-type mice. Moreover, the H. pylori–specific Th1 response was higher and the Treg and Th17 responses were lower in the spleens of infected TLR2KO mice compared to infected WT mice. Our data indicate that H. pylori mediates immune tolerance through TLR2-derived signals and inhibits Th1 immunity, thus evading host defense. TLR2 may be an important target in the modulation of the host response to H. pylori.

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Helicobacter pylori‐Pulsed Dendritic Cells Induce H. pylori‐Specific Immunity in Mice

Abstract: Background-The growing concern over the emergence of antibiotic-resistant Helicobacter pylori infection is propelling the development of an efficacious vaccine to control this highly adaptive organism.

Cited by 16 publications

References 23 publications

Helicobacter pylori Immune Escape Is Mediated by Dendritic Cell–Induced Treg Skewing and Th17 Suppression in Mice

Helicobacter pylori Immune Escape Is Mediated by Dendritic Cell–Induced Treg Skewing and Th17 Suppression in Mice

IRAK-M modulates expression of IL-10 and cell surface markers CD80 and MHC II after bacterial re-stimulation of tolerized dendritic cells

TLR2 Mediates Helicobacter pylori–Induced Tolerogenic Immune Response in Mice

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