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40‐ O ‐[2‐Hydroxyethyl]rapamycin modulates human dendritic cell function during exposure to Aspergillus fumigatus
Author(s) -
Bauer Ruth,
Mezger Markus,
Blockhaus Christian,
Schmitt AnnaLena,
Kurzai Oliver,
Einsele Hermann,
Loeffler Juergen
Publication year - 2012
Publication title -
journal of basic microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.58
H-Index - 54
eISSN - 1521-4028
pISSN - 0233-111X
DOI - 10.1002/jobm.201100071
Subject(s) - aspergillus fumigatus , cd80 , tlr2 , cd86 , dendritic cell , biology , acquired immune system , immune system , immunology , t cell , microbiology and biotechnology , innate immune system , cd40 , cytotoxic t cell , in vitro , biochemistry
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. (© 2012 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)