title: Probiotic Gut Microbiota Isolate Interacts with Dendritic Cells via Glycosylated Heterotrimeric Pili.
abstract: Mapping of the microbial molecules underlying microbiota-host interactions is key to understand how microbiota preserve mucosal homeostasis. A pivotal family of such bacterial molecules are pili. Pili are proteinaceous cell wall appendages with a well-documented role in adhesion, whilst their role in immune interaction with the host is less established. Gram-positive pili are often posttranslationally modified by sortase-specific cleavage reactions and the formation of intramolecular peptide bonds. Here we report glycosylation as a new level of posttranslational modification of sortase-dependent pili of a beneficial microbiota species and its role in immune modulation. We focused on the SpaCBA pili of the model probiotic and beneficial human gut microbiota isolate Lactobacillus rhamnosus GG. A unique combination of molecular techniques, nanoscale mechanical and immunological approaches led to the identification of mannose and fucose residues on the SpaCBA pili. These glycans on the pili are recognized by human dendritic cells via the C-type lectin receptor DC-SIGN, a key carbohydrate-dependent immune tailoring pattern recognition receptor. This specific lectin-sugar interaction is moreover of functional importance and modulated the cytokine response of dendritic cells. This provides insight into the direct role bacterial glycoproteins can play in the immunomodulation of the host. Modification of the complex heterotrimeric pili of a model probiotic and microbiota isolate with mannose and fucose is of importance for the functional interaction with the host immune lectin receptor DC-SIGN on human dendritic cells. Our findings shed light on the yet underappreciated role of glycoconjugates in bacteria-host interactions.
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium.|Department of Bioscience Engineering, Environmental Ecology & Applied Microbiology, University of Antwerp, Antwerp, Belgium.|Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Hanne L P
authors.initials: HL
authors.lastname: Tytgat
authors.affiliation: Academic Medical Center, Department of Experimental Immunology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Nienke H
authors.initials: NH
authors.lastname: van Teijlingen
authors.affiliation: Institute of Life Sciences, Université Catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Ruby May A
authors.initials: RM
authors.lastname: Sullan
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: François P
authors.initials: FP
authors.lastname: Douillard
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Pia
authors.initials: P
authors.lastname: Rasinkangas
authors.affiliation: Immunobiology Research Program and Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
authors.forename: Marcel
authors.initials: M
authors.lastname: Messing
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Justus
authors.initials: J
authors.lastname: Reunanen
authors.affiliation: Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.
authors.forename: Reetta
authors.initials: R
authors.lastname: Satokari
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium.
authors.forename: Jos
authors.initials: J
authors.lastname: Vanderleyden
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Yves F
authors.initials: YF
authors.lastname: Dufrêne
authors.affiliation: Academic Medical Center, Department of Experimental Immunology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Teunis B H
authors.initials: TB
authors.lastname: Geijtenbeek
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.|Department of Veterinary Biosciences, University of Helsinki, Helsinki, Finland.|Immunobiology Research Program and Department of Bacteriology and Immunology, University of Helsinki, Helsinki, Finland.
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
authors.affiliation: Centre of Microbial and Plant Genetics, KU Leuven, Leuven, Belgium.|Department of Bioscience Engineering, Environmental Ecology & Applied Microbiology, University of Antwerp, Antwerp, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Lebeer
mesh_terms: D001422:Bacterial Adhesion / Q000502:physiology; D001426:Bacterial Proteins / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D010861:Fimbriae, Bacterial / Q000378:metabolism*; D000069196:Gastrointestinal Microbiome / Q000502:physiology*; D006031:Glycosylation; D006801:Humans; D052201:Lacticaseibacillus rhamnosus / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins