Impaired killing of Candida albicans by granulocytes mobilized for transfusion purposes: a role for granule components

Haematologica
Roel P GazendamTaco W Kuijpers

Abstract

Granulocyte transfusions are used to treat neutropenic patients with life-threatening bacterial or fungal infections that do not respond to anti-microbial drugs. Donor neutrophils that have been mobilized with granulocyte-colony stimulating factor (G-CSF) and dexamethasone are functional in terms of antibacterial activity, but less is known about their fungal killing capacity. We investigated the neutrophil-mediated cytotoxic response against C. albicans and A. fumigatus in detail. Whereas G-CSF/dexamethasone-mobilized neutrophils appeared less mature as compared to neutrophils from untreated controls, these cells exhibited normal ROS production by the NADPH oxidase system and an unaltered granule mobilization capacity upon stimulation. G-CSF/dexamethasone-mobilized neutrophils efficiently inhibited A. fumigatus germination and killed Aspergillus and Candida hyphae, but the killing of C. albicans yeasts was distinctly impaired. Following normal Candida phagocytosis, analysis by mass spectrometry of purified phagosomes after fusion with granules demonstrated that major constituents of the antimicrobial granule components, including major basic protein (MBP), were reduced. Purified MBP showed candidacidal activity, and neutrophil...Continue Reading

Citations

Aug 26, 2016·Immunological Reviews·Roel P GazendamTaco W Kuijpers
Dec 15, 2016·The Journal of Allergy and Clinical Immunology·Taco W KuijpersTimo K van den Berg
Jun 9, 2018·Arteriosclerosis, Thrombosis, and Vascular Biology·Maaike SchillemansRuben Bierings
Nov 12, 2019·EMBO Molecular Medicine·Agata SzadeAlicja Józkowicz
Feb 7, 2020·International Journal of Molecular Sciences·Marten HansenEwa Rollmann
Jun 6, 2018·Frontiers in Cellular and Infection Microbiology·Dominik RufJohannes Wagener
Aug 22, 2017·Journal of Proteome Research·Eva StokhuijzenAlexander Benjamin Meijer
Sep 17, 2017·Cytotherapy·Juan Gea-Banacloche

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