Aspergillus fumigatus conidia inhibit tumour necrosis factor- or staurosporine-induced apoptosis in epithelial cells.
A major innate immune response to inhaled conidia of the opportunistic pathogen Aspergillus fumigatus (Af) is the synthesis of pro-inflammatory cytokines, which include tumour necrosis factor (TNF)-alpha, a known inducer of apoptosis. Modulation of host cell apoptosis has been reported to be one of the mechanisms whereby pathogens overcome host cell defences. Our study was designed to investigate whether or not Af conidia could modulate apoptosis induced by TNF-alpha or staurosporine (STS). Exposure of epithelial cells treated by these inducers and exposed to Af conidia decreased the number of apoptotic cells detected by Annexin V staining, analysis of nuclear morphology, terminal deoxynucleotidyl transferase-mediated fluorescein-dUTP nick end-labelling reaction and immunoblotting. Inhibition of apoptosis by Af conidia was seen in cells of the A549 pneumocyte II line, human tracheal epithelial 16HBE and primary human respiratory cells. Inhibition of apoptosis by Af conidia was also observed when apoptosis was induced by co-cultivating A549 cells with activated human alveolar macrophages. Unlike Af conidia, conidia of Cladosporium cladosporioides as well as latex beads or killed Af conidia have no inhibitory effect on TNF-alpha or STS-induced apoptosis. For TNF-induced apoptosis, the observed anti-apoptotic effect of Af conidia was found to be associated with a significant reduction of caspase-3.
Berkova
Nadia
N
INRA, AFSSA, ENVA, UPVM, UMR 956; 22 rue Curie, Maisons Alfort Cedex F-94700, France. nberkova@vet-alfort.fr
Lair-Fulleringer
Sybille
S
Féménia
Françoise
F
Huet
Dominique
D
Wagner
Marie-Christine
MC
Gorna
Kamila
K
Tournier
Frédéric
F
Ibrahim-Granet
Oumaïma
O
Guillot
Jacques
J
Chermette
René
R
Boireau
Pascal
P
Latgé
Jean-Paul
JP
D017209:Apoptosis / Q000187:drug effects* / Q000276:immunology; D001228:Aspergillosis / Q000276:immunology; D001232:Aspergillus fumigatus / Q000276:immunology*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D019311:Staurosporine / Q000494:pharmacology*; D014132:Trachea / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
D004791:Enzyme Inhibitors; D014409:Tumor Necrosis Factor-alpha; D019311:Staurosporine