Helicobacter pylori glycan biosynthesis modulates host immune cell recognition and response
IntroductionThe pathogenic bacterium Helicobacter pylori has evolved glycan-mediated mechanisms to evade host immune defenses. This study tests the hypothesis that genetic disruption of H. pylori glycan biosynthesis alters immune recognition and response by human gastric epithelial cells and monocyt...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-03-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1377077/full |
| _version_ | 1797256514189131776 |
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| author | Katharine A. Barrett Francis Jacob Kassama William Surks Andrew J. Mulholland Karen D. Moulton Danielle H. Dube |
| author_facet | Katharine A. Barrett Francis Jacob Kassama William Surks Andrew J. Mulholland Karen D. Moulton Danielle H. Dube |
| author_sort | Katharine A. Barrett |
| collection | DOAJ |
| description | IntroductionThe pathogenic bacterium Helicobacter pylori has evolved glycan-mediated mechanisms to evade host immune defenses. This study tests the hypothesis that genetic disruption of H. pylori glycan biosynthesis alters immune recognition and response by human gastric epithelial cells and monocyte-derived dendritic cells.MethodsTo test this hypothesis, human cell lines were challenged with wildtype H. pylori alongside an array of H. pylori glycosylation mutants. The relative levels of immune response were measured via immature dendritic cell maturation and cytokine secretion.ResultsOur findings indicate that disruption of lipopolysaccharide biosynthesis diminishes gastric cytokine production, without disrupting dendritic cell recognition and activation. In contrast, variable immune responses were observed in protein glycosylation mutants which prompted us to test the hypothesis that phase variation plays a role in regulating bacterial cell surface glycosylation and subsequent immune recognition. Lewis antigen presentation does not correlate with extent of immune response, while the extent of lipopolysaccharide O-antigen elaboration does.DiscussionThe outcomes of this study demonstrate that H. pylori glycans modulate the host immune response. This work provides a foundation to pursue immune-based tailoring of bacterial glycans towards modulating immunogenicity of microbial pathogens. |
| first_indexed | 2024-04-24T22:22:57Z |
| format | Article |
| id | doaj.art-e690178a884a41e28a98a60f5f828bf9 |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-04-24T22:22:57Z |
| publishDate | 2024-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-e690178a884a41e28a98a60f5f828bf92024-03-20T05:15:30ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882024-03-011410.3389/fcimb.2024.13770771377077Helicobacter pylori glycan biosynthesis modulates host immune cell recognition and responseKatharine A. BarrettFrancis Jacob KassamaWilliam SurksAndrew J. MulhollandKaren D. MoultonDanielle H. DubeIntroductionThe pathogenic bacterium Helicobacter pylori has evolved glycan-mediated mechanisms to evade host immune defenses. This study tests the hypothesis that genetic disruption of H. pylori glycan biosynthesis alters immune recognition and response by human gastric epithelial cells and monocyte-derived dendritic cells.MethodsTo test this hypothesis, human cell lines were challenged with wildtype H. pylori alongside an array of H. pylori glycosylation mutants. The relative levels of immune response were measured via immature dendritic cell maturation and cytokine secretion.ResultsOur findings indicate that disruption of lipopolysaccharide biosynthesis diminishes gastric cytokine production, without disrupting dendritic cell recognition and activation. In contrast, variable immune responses were observed in protein glycosylation mutants which prompted us to test the hypothesis that phase variation plays a role in regulating bacterial cell surface glycosylation and subsequent immune recognition. Lewis antigen presentation does not correlate with extent of immune response, while the extent of lipopolysaccharide O-antigen elaboration does.DiscussionThe outcomes of this study demonstrate that H. pylori glycans modulate the host immune response. This work provides a foundation to pursue immune-based tailoring of bacterial glycans towards modulating immunogenicity of microbial pathogens.https://www.frontiersin.org/articles/10.3389/fcimb.2024.1377077/fullglycanimmunologyglycosylation mutantphase variationHelicobacter pylorimetabolic labeling |
| spellingShingle | Katharine A. Barrett Francis Jacob Kassama William Surks Andrew J. Mulholland Karen D. Moulton Danielle H. Dube Helicobacter pylori glycan biosynthesis modulates host immune cell recognition and response Frontiers in Cellular and Infection Microbiology glycan immunology glycosylation mutant phase variation Helicobacter pylori metabolic labeling |
| title | Helicobacter pylori glycan biosynthesis modulates host immune cell recognition and response |
| title_full | Helicobacter pylori glycan biosynthesis modulates host immune cell recognition and response |
| title_fullStr | Helicobacter pylori glycan biosynthesis modulates host immune cell recognition and response |
| title_full_unstemmed | Helicobacter pylori glycan biosynthesis modulates host immune cell recognition and response |
| title_short | Helicobacter pylori glycan biosynthesis modulates host immune cell recognition and response |
| title_sort | helicobacter pylori glycan biosynthesis modulates host immune cell recognition and response |
| topic | glycan immunology glycosylation mutant phase variation Helicobacter pylori metabolic labeling |
| url | https://www.frontiersin.org/articles/10.3389/fcimb.2024.1377077/full |
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