Probiotic Gut Microbiota Isolate Interacts with Dendritic Cells via Glycosylated Heterotrimeric Pili

PLoS One. 2016 Mar 17;11(3):e0151824. doi: 10.1371/journal.pone.0151824. eCollection 2016.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Adhesion / physiology
  • Bacterial Proteins / metabolism*
  • Dendritic Cells / metabolism*
  • Fimbriae, Bacterial / metabolism*
  • Gastrointestinal Microbiome / physiology*
  • Glycosylation
  • Humans
  • Lacticaseibacillus rhamnosus / metabolism*


  • Bacterial Proteins

Grants and funding

HLPT acknowledges the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT Vlaanderen) for her PhD scholarship. SL holds a ‘Krediet aan Navorsers’ (28960) from FWO-Vlaanderen. JV, SL and HLPT are grateful for the financial support of the University of Leuven via PF3M100234 and UAntwerp via BOF and IOF-SBO funding. NHvT is sponsored by the AMC PhD Scholarship. TBHG is sponsored by NWO; VICI 918.10.619. PR and FPD are funded by the European Research Council grant MicrobesInside (250172) of WMdV. JR, RS and WMdV want to acknowledge the financial support from the Academy of Finland (138902, 254439 and 141140). Work at UCLouvain was supported by the National Fund for Scientific Research (FNRS), the UCLouvain (Fondation Louvain-Prix de Merre), the Federal Office for Scientific, Technical and Cultural Affairs (Interuniversity Poles of Attraction Programme), and the Research Department of the Communauté française de Belgique (Concerted Research Action). YFD is a research Director of the FNRS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.