Article (Scientific journals)
Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.
Drewniak, Agata; Gazendam, Roel P.; Tool, Anton T. J. et al.
2013In Blood, 121 (13), p. 2385-2392
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Keywords :
Adolescent; Brain Diseases/diagnosis/etiology/immunology; CARD Signaling Adaptor Proteins/deficiency/genetics/immunology; Candida albicans/immunology/isolation & purification; Candidiasis, Invasive/complications/genetics/immunology; Cells, Cultured; Cytophagocytosis/genetics/immunology; Female; Humans; Immunity, Innate/genetics/physiology; Neutrophils/immunology
Abstract :
[en] Caspase recruitment domain-containing protein 9 (CARD9) is an adaptor molecule in the cytosol of myeloid cells, required for induction of T-helper cells producing interleukin-17 (Th17 cells) and important in antifungal immunity. In a patient suffering from Candida dubliniensis meningoencephalitis, mutations in the CARD9 gene were found to result in the loss of protein expression. Apart from the reduced numbers of CD4(+) Th17 lymphocytes, we identified a lack of monocyte-derived cytokines in response to Candida strains. Importantly, CARD9-deficient neutrophils showed a selective Candida albicans killing defect with abnormal ultrastructural phagolysosomes and outgrowth of hyphae. The neutrophil killing defect was independent of the generation of reactive oxygen species by the reduced NAD phosphate oxidase system. Taken together, this demonstrates that human CARD9 deficiency results in selective defect in the host defense against invasive fungal infection, caused by an impaired phagocyte killing.
Disciplines :
Human health sciences: Multidisciplinary, general & others
Author, co-author :
Drewniak, Agata
Gazendam, Roel P.
Tool, Anton T. J.
van Houdt, Michel
Jansen, Machiel H.
van Hamme, John L.
van Leeuwen, Ester M. M.
Roos, Dirk
Scalais, Emmanuel
De Beaufort, Carine ;  University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB)
Janssen, Hans
van den Berg, Timo K.
Kuijpers, Taco W.
More authors (3 more) Less
External co-authors :
yes
Language :
English
Title :
Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.
Publication date :
28 March 2013
Journal title :
Blood
ISSN :
1528-0020
Publisher :
American Society of Hematology, Washington, United States - District of Columbia
Volume :
121
Issue :
13
Pages :
2385-2392
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBilu :
since 30 April 2016

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