Neutrophil microbial killing mechanisms lessons learned from primary immunodeficiencies
Neutrophils are important cells in the prevention of invasive bacterial and fungal infection. Neutrophils derived from knock-out mice have emonstrated the role of pathogen recognition receptors (PRRs), signal transduction pathways and cytotoxicity in the antimicrobial immune response. 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. Experiments with these human “knock-out” neutrophils have expanded our knowledge about the role of PRRs 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.
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