Human NK cells develop an exhaustion phenotype during polar degranulation at the aspergillus fumigatus hyphal synapse

Title: Human NK cells develop an exhaustion phenotype during polar degranulation at the aspergillus fumigatus hyphal synapse
Authors: Santiago, V
Rezvani, K
Sekine, T
Stebbing, J
Kelleher, P
Armstrong-James, D
Item Type: Journal Article
Abstract: 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 A. fumigatus. We show that the in vitro interaction between NK cells and A. fumigatus 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 A. fumigatus. These observations suggest that A. fumigatus-mediated NK cell immunoparesis may represent an important mechanism of immune evasion during pulmonary aspergillosis.
Issue Date: 22-Oct-2018
Date of Acceptance: 21-Sep-2018
URI: http://hdl.handle.net/10044/1/64697
DOI: https://dx.doi.org/10.3389/fimmu.2018.02344
ISSN: 1664-3224
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Immunology
Volume: 9
Copyright Statement: © 2018 Santiago, Rezvani, Sekine, Stebbing, Kelleher and Armstrong-James. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY - https://creativecommons.org/licenses/by/4.0/). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: G0902260
Keywords: Science & Technology
Life Sciences & Biomedicine
Immunology
NK cells
Aspergillus fumigatus
fungal disease
immunocompromise
leukaemia
MYELOID DENDRITIC CELLS
NATURAL-KILLER-CELLS
TOLL-LIKE RECEPTOR-9
INVASIVE ASPERGILLOSIS
DEOXYNUCLEIC ACIDS
HOST-DEFENSE
IFN-GAMMA
CPG-DNA
ACTIVATION
RELEASE
Aspergillus fumigatus
NK cells
fungal disease
immunocompromise
leukaemia
Science & Technology
Life Sciences & Biomedicine
Immunology
NK cells
Aspergillus fumigatus
fungal disease
immunocompromise
leukaemia
MYELOID DENDRITIC CELLS
NATURAL-KILLER-CELLS
TOLL-LIKE RECEPTOR-9
INVASIVE ASPERGILLOSIS
DEOXYNUCLEIC ACIDS
HOST-DEFENSE
IFN-GAMMA
CPG-DNA
ACTIVATION
RELEASE
Publication Status: Published
Article Number: 2344
Online Publication Date: 2018-10-22
Appears in Collections:National Heart and Lung Institute
Department of Medicine
Faculty of Medicine



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