Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency

Agata 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

Research output: Contribution to journalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)2385-92
Number of pages8
JournalBlood
Volume121
Issue number13
DOIs
Publication statusPublished - 28 Mar 2013

Cite this

Drewniak, A., Gazendam, R. P., Tool, A. T. J., van Houdt, M., Jansen, M. H., van Hamme, J. L., ... Kuijpers, T. W. (2013). Invasive fungal infection and impaired neutrophil killing in human CARD9 deficiency. Blood, 121(13), 2385-92. https://doi.org/10.1182/blood-2012-08-450551