Document Detail


Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.
MedLine Citation:
PMID:  23335372     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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 IL-17 (Th17 cells) and important in anti-fungal 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 (ROS) by the NADPH 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.
Authors:
Agata A Drewniak; Roel P Gazendam; Anton T J Tool; Michel van Houdt; Machiel H Jansen; John L van Hamme; Ester M M van Leeuwen; Dirk Roos; Emmanuel Scalais; Carine de Beaufort; Hans Janssen; Timo K van den Berg; Taco W Kuijpers
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-18
Journal Detail:
Title:  Blood     Volume:  -     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Netherlands;
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