Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency.
Blood
; 121(13): 2385-92, 2013 Mar 28.
Article
em En
| MEDLINE
| ID: mdl-23335372
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Adaptadoras de Sinalização CARD
/
Candidíase Invasiva
/
Neutrófilos
Tipo de estudo:
Diagnostic_studies
/
Etiology_studies
/
Prognostic_studies
Limite:
Adolescent
/
Female
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article