title: 40-O -[2-Hydroxyethyl]rapamycin modulates human dendritic cell function during exposure to Aspergillus fumigatus.
abstract: 40-O -[2-Hydroxyethyl]rapamycin (RAD), a novel derivative of the immunosuppressive drug rapamycin, was analyzed for its immunomodulatory influence during the interaction of human monocyte-derived dendritic cells (moDC) with Aspergillus fumigatus. RAD is clinically used to prevent graft-versus -host disease as well as solid organ and bone marrow transplant rejection. However, it may constitute a risk factor for the development of opportunistic infections, such as invasive aspergillosis which is mainly caused by the most common airborne fungal pathogen A. fumigatus. moDC were generated in the presence or absence of RAD. In this setting, RAD had various modulating effects on the immune function of DC. A decrease of pro- and anti-inflammatory cytokines (IL-12, TNF-α, CCL20, IL-10) was observed. Furthermore, RAD reduced the expression of innate immunity receptors (TLR2, TLR4, dectin-1), impaired the maturation capacity of moDC observed through the reduction of costimulatory factors (CD40, CD80, CD83, CD86), and impaired their capacity to phagocytose and damage A. fumigatus. These data demonstrate that RAD influences the differentiation of DC. RAD modulates the cytokine response of DC to A. fumigatus and reduces their ability to kill germ tubes. Thus, RAD treatment might affect the risk of invasive aspergillosis independently of its capacity of blocking T cell activation.
authors.affiliation: Universität Würzburg, Medizinische Klinik & Poliklinik II, Würzburg, Germany.
authors.forename: Ruth
authors.initials: R
authors.lastname: Bauer
authors.forename: Markus
authors.initials: M
authors.lastname: Mezger
authors.forename: Christian
authors.initials: C
authors.lastname: Blockhaus
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Schmitt
authors.forename: Oliver
authors.initials: O
authors.lastname: Kurzai
authors.forename: Hermann
authors.initials: H
authors.lastname: Einsele
authors.forename: Juergen
authors.initials: J
authors.lastname: Loeffler
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001232:Aspergillus fumigatus / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology* / Q000502:physiology; D000068338:Everolimus; D006805:Human Experimentation; D006801:Humans; D007166:Immunosuppressive Agents / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D016207:Cytokines; D007166:Immunosuppressive Agents; D011971:Receptors, Immunologic; D000068338:Everolimus; D020123:Sirolimus