Two independent killing mechanisms of Candida albicans by human neutrophils: evidence from innate immunity defects

Roel P Gazendam, John L van Hamme, Anton T J Tool, Michel van Houdt, Paul J J H Verkuijlen, Martin Herbst, Johannes G Liese, Frank L van de Veerdonk, Dirk Roos, Timo K van den Berg, Taco W Kuijpers

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Invasive fungal infections, accompanied by high rates of mortality, represent an increasing problem in medicine. Neutrophils are the major effector immune cells in fungal killing. Based on studies with neutrophils from patients with defined genetic defects, we provide evidence that human neutrophils use 2 distinct and independent phagolysosomal mechanisms to kill Candida albicans. The first mechanism for the killing of unopsonized C albicans was found to be dependent on complement receptor 3 (CR3) and the signaling proteins phosphatidylinositol-3-kinase and caspase recruitment domain-containing protein 9 (CARD9), but was independent of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity. The second mechanism for the killing of opsonized C albicans was strictly dependent on Fcγ receptors, protein kinase C (PKC), and reactive oxygen species production by the NADPH oxidase system. Each of the 2 pathways of Candida killing required Syk tyrosine kinase activity, but dectin-1 was dispensable for both of them. These data provide an explanation for the variable clinical presentation of fungal infection in patients suffering from different immune defects, including dectin-1 deficiency, CARD9 deficiency, or chronic granulomatous disease.

Original languageEnglish
Pages (from-to)590-7
Number of pages8
JournalBlood
Volume124
Issue number4
DOIs
Publication statusPublished - 24 Jul 2014

Cite this

Gazendam, R. P., van Hamme, J. L., Tool, A. T. J., van Houdt, M., Verkuijlen, P. J. J. H., Herbst, M., ... Kuijpers, T. W. (2014). Two independent killing mechanisms of Candida albicans by human neutrophils: evidence from innate immunity defects. Blood, 124(4), 590-7. https://doi.org/10.1182/blood-2014-01-551473