Thesis Roel Gazendam

On 28 September 2016 Roel Gazendam defended his thesis ´Neutrophil microbial killing mechanisms. Lessons learned from primary immunodeficiencies´ at the University of Amsterdam.

He was awarderd the doctorate cum laude.

Promotor: prof TW Kuijpers MD PhD
Copromotores: TK van den Berg PhD and prof D Roos PhD

The research for this thesis was conducted at the Dept of Blood Cell Research of Sanquin Research and was financially supported by the Landsteiner Foundation for Blood Transfusion Research (LSBR) and Sanquin.

Summary

Humans and microbes have a balanced and longstanding relationship. Immunosuppresive therapies and primary immunodeficiencies (PIDs) may disturb this balance and result in infection. Patients with neutropenia or PIDs with neutrophil functional defects, including Chronic Granulomatous Disease (CGD), are susceptible to invasive fungal infections, accompanied by high rates of mortality. Neutrophils are the first line of defense, and important effector cells in the killing of invading pathogens and prevention of invasive infections. 
We have studied in this thesis the antimicrobial function of neutrophils from patients with novel primary immunodeficiencies (PIDs), resulting in a susceptibility to bacterial and fungal infections. In additition, the antimicrobial function of G-CSF/dexamethasone-mobilized neutrophils used for transfusion purposes was determined. Experiments with these human “knock-out” neutrophils have expanded our knowledge about the role of Pathogen Recognition Receptors and signaling in microbial killing in humans. Neutrophils have distinct mechanisms for the killing of S. aureus, E. coli, C. albicans or A. fumigatus conidia and hyphae. The formation of Neutrophil Extracellular Traps (NETs) is not required for the killing of C. albicans or A. fumigatus. G-CSF/dexamethasone-mobilized neutrophils used for transfusion purposes, are impaired in Candida yeast killing, but normally kill bacterial and fungal pathogens.