AUTHOR=Barrett Katharine A. , Kassama Francis Jacob , Surks William , Mulholland Andrew J. , Moulton Karen D. , Dube Danielle H.
TITLE=Helicobacter pylori glycan biosynthesis modulates host immune cell recognition and response
JOURNAL=Frontiers in Cellular and Infection Microbiology
VOLUME=14
YEAR=2024
URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2024.1377077
DOI=10.3389/fcimb.2024.1377077
ISSN=2235-2988
ABSTRACT=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.