Human natural killer cells and Aspergillus fumigatus differentially influence their gene expression profile

Thomas Lehrnbecher


Background: Natural Killer (NK) cells are active against a variety of pathogens including Aspergillus
fumigatus, which, in turn produces proteins to impair host defense and to facilitate tissue invasion.
However, little is known on the interaction of NK cells and A. fumigatus.
Material/methods: We investigated the mutual influence of gene expression profiles of human NK
cells and A. fumigatus. Freshly isolated and interleukin-2 prestimulated human NK cells were
coincubated with A. fumigatus and the gene expression of selected genes of both NK cells and the
fungus was assessed at several time points by quantitative real-time PCR.
Results: Our data demonstrate that A. fumigatus down-regulates mRNA levels of cytotoxic molecules
such as perforin or granzyme B in human NK cells, but increases the gene expression of proinflammatory
molecules such as interferon-gamma, tumor-necrosis factor α, and macrophage
inflammatory proteins 1α/1β. In contrast, NK cells did not exhibit major impact on fungal gene
expression of molecules such as superoxide dismutases, catalases, and mycotoxins, but moderately
up-regulates mRNA levels of stress related molecules such as heat shock protein90 and alkaline
phosphatase 1.
Conclusions: Our results significantly differ from the reported findings using a setting of A. fumigatus
coincubated with neutrophils, which suggests that the fungus differentially regulates its gene
expression depending on the mechanism of the fungal damage (e.g., reactive oxygen species by
neutrophils or perforin by NK cells). This, in turn, gives further insight into the complex interaction of
host immune cells and A. fumigatus and might have important implications for immunotherapeutic
approaches using neutrophils or NK cells.



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26th European Congress of Clinical Microbiology and Infectious Diseases
    • ECCMID 26th (2016)