Multivalent Choline Dendrimers Increase Phagocytosis of Streptococcus pneumoniae R6 by Microglial Cells

Background: Pneumococcal virulence factors common to all serotypes, such as choline-binding proteins (CBPs), are promising therapeutic targets in pneumococcal infections. We studied the effect of a choline dendrimer with maximized binding affinity/specificity for CBPs on microglia-mediated pneumococ...

Full description

Bibliographic Details
Authors: Ribes, Sandra, Riegelmann, Jörn, Redlich, Sandra, Maestro García-Donas, Beatriz, de Waal, Bas, Meijer, E.W., Sanz, Jesús M., Nau, Roland
Format: article
Publication Date:2013
Country:España
Institution:Universidad Miguel Hernández de Elche
Repository:REDIUMH. Depósito Digital de la UMH
OAI Identifier:oai:dspace.umh.es:11000/30957
Online Access:https://hdl.handle.net/11000/30957
Access Level:Open access
Keyword:Choline-binding proteins
Streptococcus pneumoniae
Dendrimer
Phagocytosis
Microglia
Description
Summary:Background: Pneumococcal virulence factors common to all serotypes, such as choline-binding proteins (CBPs), are promising therapeutic targets in pneumococcal infections. We studied the effect of a choline dendrimer with maximized binding affinity/specificity for CBPs on microglia-mediated pneumococcal phagocytosis. Methods: Pneumoccocal cultures were exposed to dendrimers containing 8 choline end groups or amino groups as controls, either from the beginning of bacterial growth or at the late exponential phase. The effect of long/short co-incubation was assessed in terms of bacterial morphological changes and increase in bacterial uptake by primary microglial cultures. Results: Inhibiting CBPs by micromolar concentrations of a choline dendrimer caused the formation of long pneumococcal chains that were readily phagocytosed by microglia. Enhanced phagocytosis was dendrimer dose-dependent. Long bacteria-dendrimer co-incubation (14 h) resulted in a higher bacterial uptake than short co-incubation (2 h; p < 0.001). Conclusions: Multivalent dendrimers containing choline end groups are promising antimicrobial agents for the management of pneumococcal diseases.