Background: Since Natural Killer (NK) cells kill tumor cells and combat infections, there is growing interest in adoptively transferring NK cells to allogeneic hematopoietic stem cell recipients. We recently demonstrated that human NK cells exhibit antifungal activity against Aspergillus spp. Unfortunately, the activity of human NK cells against zygomycetes is unknown, which increasingly cause invasive fungal infections resistant to most antifungal compound. Methods: The interaction of freshly isolated and IL-2 prestimulated human NK cells and R. oryzae was evaluated in vitro by means of flow cytometry and XTT assay. Results: Unstimulated freshly isolated human NK cells are activated by Rhizopus hyphae demonstrated by up-regulation of the activation marker CD69. In contrast, resting conidia and culture supernatant of R. oryzae hyphae did not activate unstimulated NK cells, indicating that cell-fungus contact is essential for NK cell activation. The results of the XTT assay showed that both unstimulated and IL-2 pre-stimulated human NK cells kill R. oryzae hyphae, but do not affect resting conidia. Killing of R. oryzae hyphae is also induced by isolated human perforin. In addition, blocking of the perforin mediated cytotoxicity of NK cells via concanamycin A significantly reduced the hyphal damage, indicating that perforin is an important mediator of anti-Rhizopus activity of NK cells. Conclusion: Since NK cells demonstrate in vitro antifungal activity against Aspergillus spp. and zygomycetes, adoptively transferred human NK cells may be a potential antifungal tool in the transplant setting. However, before designing clinical trials, our results have to be validated in animal models.
Full conference title:
Trends in Medical Mycology, 5th
- TIMM 5th (2013)