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Kupfahl C, Geginat G, Hof H.
Gliotoxin - mediated suppression of innate and adaptive immune
functions directed against Listeria monocytogenes.
Med Mycol. 2006 Nov;44(7):591-9.
Institut für Medizinische Mikrobiologie und Hygiene, Fakultät für
klinische Medizin Mannheim der Universität Heidelberg, Theodor-Kutzer-Ufer
1-3, 68167, Mannheim, Germany.
claudio.kupfahl@imh.ma.uni-heidelberg.de
Gliotoxin is an immunosuppressive apoptogenic mycotoxin produced by a
number of fungi including important human pathogens as Aspergillus
fumigatus. In order to elucidate the potential role of gliotoxin as
immunoevasive fungal virulence factor we studied the effects of
gliotoxin on the innate and adaptive T cell-mediated immune response
against the facultatively intracellular bacterium Listeria monocytogenes.
Gliotoxin induced apoptosis of bone marrow-derived macrophages,
dendritic cells and CD8 T cells in a dose- and cell type-dependent
manner. In vitro the apoptogenic effect of gliotoxin correlated with a
strong reduction of TNF-alpha and interleukin (IL)-12 production by
dendritic cells and bone marrow-derived macrophages infected with L.
monocytogenes and in the case of infected macrophages also in reduced
NO-production and recognition by L. monocytogenes-specific CD8 T cells.
Further gliotoxin pre-treatment of CD8 T cells reduced target cell lysis.
In vivo, treatment of mice with gliotoxin increased the bacterial burden
during the innate and the adaptive phase of primary L. monocytogenes
infection. Taken together, these results demonstrate the suppressive
effects of gliotoxin on the innate and also on the adaptive T
cell-mediated antilisterial immunity.
PMID: 17071552 |
