International Immunology Advance Access originally published online on December 15, 2005
International Immunology 2006 18(1):139-150; doi:10.1093/intimm/dxh356
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Aspergillus fumigatus conidia inhibit tumour necrosis factor- or staurosporine-induced apoptosis in epithelial cells
1 INRA, AFSSA, ENVA, UPVM, UMR 956; 22 rue Curie, Maisons Alfort Cedex F-94700, France
2 Plate-Forme de Cytométrie, Institut Pasteur, Paris, France
3 Laboratoire de Cytophysiologie et Toxicologie Cellulaire, Université Paris 7, Paris, France
4 Unité des Aspergillus, Institut Pasteur, Paris, France
5 Service de Parasitologie-Mycologie, Ecole Nationale Vétérinaire d'Alfort, 7 av de Général de Gaulle, Maisons Alfort Cedex 94704, France
Correspondence to: N. Berkova; E-mail: nberkova{at}vet-alfort.fr
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)-
, 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- 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- 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.
Keywords: apoptosis, epithelial cells, fungi, programmed cell death
* These authors made an equal contribution to this work.
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