title: Visceral Leishmaniasis Patients Display Altered Composition and Maturity of Neutrophils as well as Impaired Neutrophil Effector Functions.
abstract: Immunologically, active visceral leishmaniasis (VL) is characterized by profound immunosuppression, severe systemic inflammatory responses, and an impaired capacity to control parasite replication. Neutrophils are highly versatile cells, which play a crucial role in the induction as well as the resolution of inflammation, the control of pathogen replication, and the regulation of immune responses. Neutrophil functions have been investigated in human cutaneous leishmaniasis; however, their role in human VL is poorly understood. In the present study we evaluated the activation status and effector functions of neutrophils in patients with active VL and after successful anti-leishmanial treatment. Our results show that neutrophils are highly activated and have degranulated; high levels of arginase, myeloperoxidase, and elastase, all contained in neutrophils' granules, were found in the plasma of VL patients. In addition, we show that a large proportion of these cells are immature. We also analyzed effector functions of neutrophils that are essential for pathogen clearance and show that neutrophils have an impaired capacity to release neutrophil extracellular traps, produce reactive oxygen species, and phagocytose bacterial particles, but notLeishmaniaparasites. Our results suggest that impaired effector functions, increased activation, and immaturity of neutrophils play a key role in the pathogenesis of VL.
authors.affiliation: Department of Immunology, University of Gondar , Gondar , Ethiopia.
authors.forename: Endalew
authors.initials: E
authors.lastname: Yizengaw
authors.affiliation: Department of Immunology, University of Gondar , Gondar , Ethiopia.
authors.forename: Mulusew
authors.initials: M
authors.lastname: Getahun
authors.affiliation: Department of Immunology, University of Gondar , Gondar , Ethiopia.
authors.forename: Fitsumbrhan
authors.initials: F
authors.lastname: Tajebe
authors.affiliation: Department of Medicine, Imperial College London , London , UK.
authors.forename: Edward
authors.initials: E
authors.lastname: Cruz Cervera
authors.affiliation: Leishmaniasis Research and Treatment Centre, Gondar University , Gondar , Ethiopia.
authors.forename: Emebet
authors.initials: E
authors.lastname: Adem
authors.affiliation: Department of Immunology, University of Gondar , Gondar , Ethiopia.
authors.forename: Getnet
authors.initials: G
authors.lastname: Mesfin
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Addis Ababa University , Addis Ababa , Ethiopia.
authors.forename: Asrat
authors.initials: A
authors.lastname: Hailu
authors.affiliation: Department of Biomedical Sciences, Institute of Tropical Medicine , Antwerp , Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van der Auwera
authors.affiliation: Department of Immunology and Infection, London School of Hygiene and Tropical Medicine , London , UK.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Yardley
authors.affiliation: Department of Internal Medicine, University of Gondar , Gondar , Ethiopia.
authors.forename: Mulualem
authors.initials: M
authors.lastname: Lemma
authors.affiliation: Department of Mathematics and Statistics, University of Hasselt , Hasselt , Belgium.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Skhedy
authors.affiliation: Leishmaniasis Research and Treatment Centre, Gondar University , Gondar , Ethiopia.
authors.forename: Ermias
authors.initials: E
authors.lastname: Diro
authors.affiliation: Leishmaniasis Research and Treatment Centre, Gondar University , Gondar , Ethiopia.
authors.forename: Arega
authors.initials: A
authors.lastname: Yeshanew
authors.affiliation: Leishmaniasis Research and Treatment Centre, Gondar University , Gondar , Ethiopia.
authors.forename: Roma
authors.initials: R
authors.lastname: Melkamu
authors.affiliation: Leishmaniasis Research and Treatment Centre, Gondar University , Gondar , Ethiopia.
authors.forename: Bewketu
authors.initials: B
authors.lastname: Mengesha
authors.affiliation: Department of Cellular Immunology, Max-Planck-Institute for Immunobiology and Epigenetics , Freiburg , Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Modolell
authors.affiliation: Third Department of Medicine (Hematology, Oncology, and Pneumology), University Medical Center Mainz , Mainz , Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Munder
authors.affiliation: Department of Medicine, Imperial College London , London , UK.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Müller
authors.affiliation: Department of Medicine, Imperial College London, London, UK; Leishmaniasis Research and Treatment Centre, Gondar University, Gondar, Ethiopia.
authors.forename: Yegnasew
authors.initials: Y
authors.lastname: Takele
authors.affiliation: Department of Medicine, Imperial College London , London , UK.
authors.forename: Pascale
authors.initials: P
authors.lastname: Kropf
keywords: neutrophil extracellular traps; neutrophils; phagocytosis; reactive oxygen species; visceral leishmaniasis