title: Vitamin D₃ and phenylbutyrate promote development of a human dendritic cell subset displaying enhanced antimicrobial properties.
abstract: A promising strategy in the fight against multidrug-resistant pathogens is the induction of endogenous AMPs, with compounds such as VitD₃ and PBA. These compounds display an array of immunomodulatory effects that remain to be investigated in further detail to establish their role in the clearance of infection and possible modulation of AMP expression. Here, we have investigated the effects of VitD₃ and PBA on human monocyte-DC differentiation and found that VitD₃ and PBA promote the development of a stretched CD14⁺/CD1a⁻ DC subset. This subset produced enhanced levels of ROS and human cathelicidin; furthermore, it displayed enhanced killing capacity of Staphylococcus aureus compared with control DCs. When experiments were performed in WT and cathelicidin-deficient mice, we established that a ROS-producing, stretched DC subset was also induced in mouse-derived cells, independent of cathelicidin expression. However, in contrast to the human DCs, enhanced cathelicidin expression and enhanced antimicrobial activities were not found in the murine VitD₃/PBA DC subset. In conclusion, the results of this study show that VitD₃ and PBA induce a human DC subset that is effective against infection. These results promote further research into the use of these compounds as an antimicrobial treatment strategy.
authors.affiliation: Departments of Physiology and Pharmacology and anne.van.der.does@ki.se.
authors.forename: Anne M
authors.initials: AM
authors.lastname: van der Does
authors.affiliation: Departments of Physiology and Pharmacology and.
authors.forename: Ellinor
authors.initials: E
authors.lastname: Kenne
authors.affiliation: Departments of Physiology and Pharmacology and.
authors.forename: Ella
authors.initials: E
authors.lastname: Koppelaar
authors.affiliation: Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Birgitta
authors.initials: B
authors.lastname: Agerberth
authors.affiliation: Departments of Physiology and Pharmacology and.
authors.forename: Lennart
authors.initials: L
authors.lastname: Lindbom
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000494:pharmacology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000166:cytology; D010654:Phenylbutyrates / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; D010654:Phenylbutyrates; D017382:Reactive Oxygen Species; D002762:Cholecalciferol; C075773:4-phenylbutyric acid; D054804:Cathelicidins
keywords: cathelicidin; cell differentiation; host-defense peptides; host/pathogens interactions