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.
Highlights
Natural Killer (NK) cells are lymphocytes of the innate immune system which are able to kill their target by cytotoxic molecules such as perforin or granzyme B or by death receptor-mediated apoptosis
Western blot analysis revealed that the translation of IFN-γ occurred, but that the presence of A. fumigatus resulted in a significant intracellular accumulation of IFN-γ (Figure 1C)
A. fumigatus responds to NK cells with an up-regulation of stress related genes, whereas NK cells up-regulate in the presence of A. fumigatus www.impactjournals.com/oncotarget the gene expression of pro-inflammatory cytokines such as IFN-γ or granulocyte-macrophage colonystimulating factor (GM-CSF)
Summary
Natural Killer (NK) cells are lymphocytes of the innate immune system which are able to kill their target by cytotoxic molecules such as perforin or granzyme B or by death receptor-mediated apoptosis. The term of NK cells came from their natural ability to kill tumor cells, it has been demonstrated that NK cells exhibit cytotoxicity against virus-infected cells and bacteria, and play an important role in the antifungal host response such as against Aspergillus fumigatus, which is a major cause for morbidity and mortality in patients receiving chemotherapy for cancer or undergoing hematopoietic stem cell transplantation [2]. From the pathogens point of view, A. fumigatus produces a variety of proteins, such as proteinases or mycotoxins, all of which are important in the defense mechanisms of the fungus and tissue invasion, as they detoxify antifungal molecules produced by the host or break down the host defense barriers [4]. Given the complex nature of the host-pathogen interaction, we assessed the response of A. fumigatus to host immunity
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