Carbohydrates From Pseudomonas Aeruginosa Biofilms Interact With Immune C-Type Lectins and Interfere With Their Receptor Function

Creator(s)

Sonali Singh, University of Nottingham
Yasir Almuhanna, University of Nottingham
Mohammad Y. Alshahrani, University of Nottingham
Douglas W. Lowman, Department of Surgery and Center of Excellence in Inflammation, Infectious Disease and Immunity, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, 37614, USA.
Peter J. Rice, University of Colorado
Chris Gell, University of Nottingham
Zuchao Ma, East Tennessee State UniversityFollow
Bridget M. Graves, East Tennessee State UniversityFollow
Darryl Jackson, University of Nottingham
Kelly Lee, University of Nottingham
Rucha Juarez, University of Nottingham, Nottingham
Janice Koranteng, University of Nottingham
Sirina Muntaka, University of Nottingham
Daniel A Mitchell, University of Warwick
Ana C. Da Silva, University of Nottingham
Farah Hussain, University of Nottingham
Gokhan Yilmaz, University of Nottingham

Document Type

Article

Publication Date

12-8-2021

Description

Bacterial biofilms represent a challenge to the healthcare system because of their resilience against antimicrobials and immune attack. Biofilms consist of bacterial aggregates embedded in an extracellular polymeric substance (EPS) composed of polysaccharides, nucleic acids and proteins. We hypothesised that carbohydrates could contribute to immune recognition of Pseudomonas aeruginosa biofilms by engaging C-type lectins. Here we show binding of Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN, CD209), mannose receptor (MR, CD206) and Dectin-2 to P. aeruginosa biofilms. We also demonstrate that DC-SIGN, unlike MR and Dectin-2, recognises planktonic P. aeruginosa cultures and this interaction depends on the presence of the common polysaccharide antigen. Within biofilms DC-SIGN, Dectin-2 and MR ligands appear as discrete clusters with dispersed DC-SIGN ligands also found among bacterial aggregates. DC-SIGN, MR and Dectin-2 bind to carbohydrates purified from P. aeruginosa biofilms, particularly the high molecular weight fraction (HMW; >132,000 Da), with Ks in the nM range. These HMW carbohydrates contain 74.9-80.9% mannose, display α-mannan segments, interfere with the endocytic activity of cell-associated DC-SIGN and MR and inhibit Dectin-2-mediated cellular activation. In addition, biofilm carbohydrates reduce the association of the DC-SIGN ligand Lewis, but not fucose, to human monocyte-derived dendritic cells (moDCs), and alter moDC morphology without affecting early cytokine production in response to lipopolysaccharide or P. aeruginosa cultures. This work identifies the presence of ligands for three important C-type lectins within P. aeruginosa biofilm structures and purified biofilm carbohydrates and highlights the potential for these receptors to impact immunity to P. aeruginosa infection.

Citation Information

Singh, Sonali; Almuhanna, Yasir; Alshahrani, Mohammad Y.; Lowman, Douglas W.; Rice, Peter J.; Gell, Chris; Ma, Zuchao; Graves, Bridget M.; Jackson, Darryl; Lee, Kelly; Juarez, Rucha; Koranteng, Janice; Muntaka, Sirina; Daniel A Mitchell; Da Silva, Ana C.; Hussain, Farah; and Yilmaz, Gokhan, "Carbohydrates From Pseudomonas Aeruginosa Biofilms Interact With Immune C-Type Lectins and Interfere With Their Receptor Function" (2021). ETSU Faculty Works. 380.
https://dc.etsu.edu/etsu-works-2/380