Reference : Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.
Scientific journals : Article
Human health sciences : Multidisciplinary, general & others
http://hdl.handle.net/10993/26965
Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.
English
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 mailto [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) >]
Janssen, Hans [> >]
van den Berg, Timo K. [> >]
Kuijpers, Taco W. [> >]
28-Mar-2013
Blood
121
13
2385-2392
Yes (verified by ORBilu)
0006-4971
1528-0020
United States
[en] 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
[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.
http://hdl.handle.net/10993/26965

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