Oncotarget

Research Perspective: Immunology:

Aspergillus fumigatus responds to natural killer (NK) cells with upregulation of stress related genes and inhibits the immunoregulatory function of NK cells

Andreas Schneider, Michael Blatzer, Wilfried Posch, Ralf Schubert, Cornelia Lass-Flörl, Stanislaw Schmidt and Thomas Lehrnbecher _

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Oncotarget. 2016; 7:71062-71071. https://doi.org/10.18632/oncotarget.12616

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Abstract

Andreas Schneider1, Michael Blatzer2, Wilfried Posch2, Ralf Schubert3, Cornelia Lass-Flörl2, Stanislaw Schmidt1,* and Thomas Lehrnbecher1,*

1 Division of Pediatric Hematology and Oncology, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany

2 Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria

3 Division of Pediatric Pulmonology, Allergology and Cystic Fibrosis, Hospital for Children and Adolescents, Johann Wolfgang Goethe-University, Frankfurt, Germany

* Co-senior authors

Correspondence to:

Thomas Lehrnbecher, email:

Keywords: Aspergillus fumigatus, human natural killer cell, gene expression, perforin, cytokine, Immunology and Microbiology Section, Immune response, Immunity

Received: September 02, 2016 Accepted: September 17, 2016 Published: October 12, 2016

Abstract

Natural Killer (NK) cells are active against Aspergillus fumigatus, which in turn is able to impair the host defense. Unfortunately, little is known on the mutual interaction of NK cells and A. fumigatus. We coincubated human NK cells with A. fumigatus hyphae and assessed the gene expression and protein concentration of selected molecules. We found that A. fumigatus up-regulates the gene expression of pro-inflammatory molecules in NK cells, but inhibited the release of these molecules resulting in intracellular accumulation and limited extracellular availability. A. fumigatus down-regulatedmRNA levels of perforin in NK cells, but increased its intra- and extracellular protein concentration. The gene expression of stress related molecules of A. fumigatus such as heat shock protein hsp90 was up-regulated by human NK cells. Our data characterize for the first time the immunosuppressive effect of A. fumigatus on NK cells and may help to develop new therapeutic antifungal strategies.


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