NBEAL2 is required for neutrophil and NK cell function and pathogen defense
File(s)
Author(s)
Type
Journal Article
Abstract
Mutations in the human NBEAL2 gene cause gray platelet syndrome (GPS), a bleeding diathesis characterized by a lack of α granules in platelets. The functions of the NBEAL2 protein have not been explored outside platelet biology, but there are reports of increased frequency of infection and abnormal neutrophil morphology in patients with GPS. We therefore investigated the role of NBEAL2 in immunity by analyzing the phenotype of Nbeal2-deficient mice. We found profound abnormalities in the Nbeal2-deficient immune system, particularly in the function of neutrophils and NK cells. Phenotyping of Nbeal2-deficient neutrophils showed a severe reduction in granule contents across all granule subsets. Despite this, Nbeal2-deficient neutrophils had an enhanced phagocyte respiratory burst relative to Nbeal2-expressing neutrophils. This respiratory burst was associated with increased expression of cytosolic components of the NADPH oxidase complex. Nbeal2-deficient NK cells were also dysfunctional and showed reduced degranulation. These abnormalities were associated with increased susceptibility to both bacterial (Staphylococcus aureus) and viral (murine CMV) infection in vivo. These results define an essential role for NBEAL2 in mammalian immunity.
Date Issued
2017-09-01
Date Acceptance
2017-06-23
Citation
Journal of Clinical Investigation, 2017, 127 (9), pp.3259-3264
ISSN
0021-9738
Publisher
American Society for Clinical Investigation
Start Page
3259
End Page
3264
Journal / Book Title
Journal of Clinical Investigation
Volume
127
Issue
9
Copyright Statement
© 2017 Sowerby et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000408842300007&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Medicine, Research & Experimental
Research & Experimental Medicine
GRAY PLATELET SYNDROME
MURINE CYTOMEGALOVIRUS-INFECTION
ALPHA-GRANULES
MICE
MUTATIONS
PROTEIN
BEACH
Publication Status
Published
Date Publish Online
2017-08-07