title: Design of phosphorylated dendritic architectures to promote human monocyte activation.
abstract: 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.
authors.affiliation: INSERM 563, Centre de Physiopathologie de Toulouse-Purpan, Hôpital Purpan, BP3028, 31024 Toulouse cedex 03, France.
authors.forename: Mary
authors.initials: M
authors.lastname: Poupot
authors.forename: Laurent
authors.initials: L
authors.lastname: Griffe
authors.forename: Patrice
authors.initials: P
authors.lastname: Marchand
authors.forename: Alexandrine
authors.initials: A
authors.lastname: Maraval
authors.forename: Olivier
authors.initials: O
authors.lastname: Rolland
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martinet
authors.forename: Fatima-Ezzahra
authors.initials: FE
authors.lastname: L'Faqihi-Olive
authors.forename: Cédric-Olivier
authors.initials: CO
authors.lastname: Turrin
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Caminade
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Majoral
authors.forename: Rémy
authors.initials: R
authors.lastname: Poupot
mesh_terms: 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
chemical_list: D050091:Dendrimers; D016328:NF-kappa B; D010758:Phosphorus; D016650:Fluorescein-5-isothiocyanate