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

© 2014 by The American Society of Hematology..

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2014

Erschienen:

2014

Enthalten in:

Zur Gesamtaufnahme - volume:124

Enthalten in:

Blood - 124(2014), 4 vom: 24. Juli, Seite 590-7

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Dectin 1
EC 1.6.3.-
EC 2.7.10.1
EC 2.7.10.2
EC 2.7.11.13
FCGR1A protein, human
Intracellular Signaling Peptides and Proteins
Journal Article
Lectins, C-Type
NADPH Oxidases
Protein Kinase C
Protein-Tyrosine Kinases
Reactive Oxygen Species
Receptors, IgG
Research Support, Non-U.S. Gov't
SYK protein, human
Syk Kinase

Anmerkungen:

Date Completed 18.11.2014

Date Revised 10.04.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1182/blood-2014-01-551473

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM239366662