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Multivalent choline dendrimers increase phagocytosis of Streptococcus pneumoniae R6 by microglial cells
Sandra Ribes1, Jörn Riegelmann, Sandra Redlich
1Institute of Neuropathology, University Medical Center Göttingen, Göttingen, Germany.
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.
