Direct interaction of human NK cells with Aspergillus fumigatus induces a Th1 immune response and provokes signi64257; cant fungal killing but not via their usual cytotoxic pathways

Ref ID: 18569

Author:

M. Bouzani, M. Ok, O. Kurzai, H. Einsele, J. Loef64258; er

Author address:

Wurzburg University (Wurzburg, DE)

Full conference title:

Annual Meeting of the EBMT, 36th

Abstract:

Objectives: Invasive aspergillosis (IA), caused mainly by
Aspergillus fumigatus (AF), is a highly devastating disease
for immunosuppressed subjects. Host’s defence is principally
confi ned to innate effector cells like alveolar macrophages,
neutrophils and dendritic cells. In our study, we questioned the
possible interaction of AF with another potent component of the
innate immunity, the Natural Killer (NK) cells.
Methods: Human NK cells were isolated after magnetic depletion of the peripheral blood of volunteers and they were used
after 24h priming with 500 U/ml recombinant human interleukin
2, rhIL2. Interferon gamma (IFN-g) and Tumor Necrosis Factoralpha (TNF-a) regulation were assessed after NK-AF coculture. Fungal damage was investigated through plate killing
assays. To investigate the infl uence of rhIL2 on NK cells, plate
killing experiments were performed with resting and primed NK
cells. Transwell permeable membranes, NK cell granule depletion (treatment with strontium chloride), surface expression
of degranulation markers CD107a/b and neutralization of NK
death ligands (TNF- related apoptosis- inducing ligand [TRAIL]
and FasL) by blocking antibodies were used to evaluate the
means of interaction.
Results: Fungal germlings induced towards NK cells a Th1
immune response with upregulation of IFN-g and TNF-a
(p<0.05). NK cells displayed strong fungicidal effect against germlings (p<0.05), but they were inactive against conidia. Priming with rhIL2 (p<0.05) and direct effector-pathogen contact (p<0.001) were required for their interaction. The cytotoxic effect was not attributed neither to the release of perforingranzyme, nor to the engagement of NK cell death ligands. Conclusion: Human NK cells are stimulated in vitro by AF, which triggers a Th1 immune response and causes important fungal killing. This interaction requires priming of NK cells with rhIL2 and conditions of direct contact between NK cells and fungus. Interestingly, NK cells do not mediate their cytotoxic effect via perforin - granzyme pathway, neither through the engagement of death ligands, suggesting that another pathway is involved in NK cell - AF interaction. Our study attributes to NK cells antiAspergillus properties, suggesting them as a future potential immunotherapeutic tool against IA.

Abstract Number: O89

Conference Year: 2010

Link to conference website: NULL

New link: NULL

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