AUTHOR=Santiago Virginia , Rezvani Katayoun , Sekine Takuya , Stebbing Justin , Kelleher Peter , Armstrong-James Darius 

TITLE=Human NK Cells Develop an Exhaustion Phenotype During Polar Degranulation at the Aspergillus fumigatus Hyphal Synapse

JOURNAL=Frontiers in Immunology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.02344

DOI=10.3389/fimmu.2018.02344

ISSN=1664-3224

ABSTRACT=<p>Pulmonary aspergillosis is an opportunistic fungal infection affecting immunocompromised individuals. Increasing understanding of natural killer (NK) cell immunobiology has aroused considerable interest around the role of NK cells in pulmonary aspergillosis in the immunocompromised host. Murine studies indicate that NK cells play a critical role in pulmonary clearance of <italic>A. fumigatus</italic>. We show that the <italic>in vitro</italic> interaction between NK cells and <italic>A. fumigatus</italic> induces partial activation of NK cell immune response, characterised by low-level production of IFN-γ, TNF-α, MIP-1α, MIP-1β, and RANTES, polarisation of lytic granules and release of fungal DNA. We observed a contact-dependent down-regulation of activatory receptors NKG2D and NKp46 on the NK cell surface, and a failure of full granule release. Furthermore, the NK cell cytokine-mediated response to leukaemic cells was impaired in the presence of <italic>A. fumigatus</italic>. These observations suggest that <italic>A. fumigatus</italic>-mediated NK cell immunoparesis may represent an important mechanism of immune evasion during pulmonary aspergillosis.</p>