Design of phosphorylated dendritic architectures to promote human monocyte activation.
As first defensive line, monocytes are a pivotal cell population of innate immunity. Monocyte activation can be relevant to a range of immune conditions and responses. Here we present new insights into the activation of monocytes by a series of phosphonic acid-terminated, phosphorus-containing dendrimers. Various dendritic or subdendritic structures were synthesized and tested, revealing the basic structural requirements for monocyte activation. We showed that multivalent character and phosphonic acid capping of dendrimers are crucial for monocyte targeting and activation. Confocal videomicroscopy showed that a fluorescein-tagged dendrimer binds to isolated monocytes and gets internalized within a few seconds. We also found that dendrimers follow the phagolysosomial route during internalization by monocytes. Finally, we performed fluorescence resonance energy transfer (FRET) experiments between a specifically designed fluorescent dendrimer and phycoerythrin-coupled antibodies. We showed that the typical innate Toll-like receptor (TLR)-2 is clearly involved, but not alone, in the sensing of dendrimers by monocytes. In conclusion, phosphorus-containing dendrimers appear as precisely tunable nanobiotools able to target and activate human innate immunity and thus prove to be good candidates to develop new drugs for immunotherapies.
Poupot
Mary
M
INSERM 563, Centre de Physiopathologie de Toulouse-Purpan, Hôpital Purpan, BP3028, 31024 Toulouse cedex 03, France.
Griffe
Laurent
L
Marchand
Patrice
P
Maraval
Alexandrine
A
Rolland
Olivier
O
Martinet
Ludovic
L
L'Faqihi-Olive
Fatima-Ezzahra
FE
Turrin
Cédric-Olivier
CO
Caminade
Anne-Marie
AM
Fournié
Jean-Jacques
JJ
Majoral
Jean-Pierre
JP
Poupot
Rémy
R
D000328:Adult; D018929:Cell Culture Techniques; D050091:Dendrimers / Q000378:metabolism*; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D010587:Phagocytosis; D010758:Phosphorus / Q000378:metabolism; D010766:Phosphorylation; D021381:Protein Transport
D050091:Dendrimers; D016328:NF-kappa B; D010758:Phosphorus; D016650:Fluorescein-5-isothiocyanate