title: Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.
abstract: 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.
authors: Sanquin Research, and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: Agata
authors: A
authors: Drewniak
authors: Roel P
authors: RP
authors: Gazendam
authors: Anton T J
authors: AT
authors: Tool
authors: Michel
authors: M
authors: van Houdt
authors: Machiel H
authors: MH
authors: Jansen
authors: John L
authors: JL
authors: van Hamme
authors: Ester M M
authors: EM
authors: van Leeuwen
authors: Dirk
authors: D
authors: Roos
authors: Emmanuel
authors: E
authors: Scalais
authors: Carine
authors: C
authors: de Beaufort
authors: Hans
authors: H
authors: Janssen
authors: Timo K
authors: TK
authors: van den Berg
authors: Taco W
authors: TW
authors: Kuijpers
mesh_terms: D000293:Adolescent; D001927:Brain Diseases / Q000175:diagnosis / Q000209:etiology / Q000276:immunology; D053468:CARD Signaling Adaptor Proteins / Q000172:deficiency* / Q000235:genetics* / Q000276:immunology; D002176:Candida albicans / Q000276:immunology / Q000302:isolation & purification; D058365:Candidiasis, Invasive / Q000150:complications / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D057899:Cytophagocytosis / Q000235:genetics / Q000276:immunology; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics / Q000502:physiology; D009504:Neutrophils / Q000276:immunology*
chemical_list: D053468:CARD Signaling Adaptor Proteins; C505855:CARD9 protein, human