title: Successful Treatment of Human Visceral Leishmaniasis Restores Antigen-Specific IFN-γ, but not IL-10 Production.
abstract: One of the key immunological characteristics of active visceral leishmaniasis (VL) is a profound immunosuppression and impaired production of Interferon-γ (IFN-γ). However, recent studies from Bihar in India showed using a whole blood assay, that whole blood cells have maintained the capacity to produce IFN-γ. Here we tested the hypothesis that a population of low-density granulocytes (LDG) might contribute to T cell responses hyporesponsiveness via the release of arginase. Our results show that this population is affected by the anticoagulant used to collect blood: the frequency of LDGs is significantly lower when the blood is collected with heparin as compared to EDTA; however, the anticoagulant does not impact on the levels of arginase released. Next, we assessed the capacity of whole blood cells from patients with active VL to produce IFN-γ and IL-10 in response to antigen-specific and polyclonal activation. Our results show that whole blood cells produce low or levels below detection limit of IFN-γ and IL-10, however, after successful treatment of VL patients, these cells gradually regain their capacity to produce IFN-γ, but not IL-10, in response to activation. These results suggest that in contrast to VL patients from Bihar, India, whole blood cells from VL patients from Gondar, Ethiopia, have lost their ability to produce IFN-γ during active VL and that active disease is not associated with sustained levels of IL-10 production following stimulation.
authors.affiliation: Department of Immunology, University of Gondar, Ethiopia.
authors.forename: Emebet
authors.initials: E
authors.lastname: Adem
authors.affiliation: Department of Immunology, University of Gondar, Ethiopia.
authors.forename: Fitsumbirhan
authors.initials: F
authors.lastname: Tajebe
authors.affiliation: Department of Immunology, University of Gondar, Ethiopia.
authors.forename: Mulusew
authors.initials: M
authors.lastname: Getahun
authors.affiliation: Department of Immunology, University of Gondar, Ethiopia.
authors.forename: Amare
authors.initials: A
authors.lastname: Kiflie
authors.affiliation: Department of Internal Medicine, University of Gondar, Ethiopia.
authors.forename: Ermias
authors.initials: E
authors.lastname: Diro
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Addis Ababa University, Ethiopia.
authors.forename: Asrat
authors.initials: A
authors.lastname: Hailu
authors.affiliation: Department of Mathematics and Statistics, University of Hasselt, Belgium.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Shkedy
authors.affiliation: Leishmaniasis Research and Treatment Centre, Gondar University, Ethiopia.
authors.forename: Bewketu
authors.initials: B
authors.lastname: Mengesha
authors.affiliation: Leishmaniasis Research and Treatment Centre, Gondar University, Ethiopia.
authors.forename: Tadele
authors.initials: T
authors.lastname: Mulaw
authors.affiliation: Leishmaniasis Research and Treatment Centre, Gondar University, Ethiopia.
authors.forename: Saba
authors.initials: S
authors.lastname: Atnafu
authors.affiliation: Department of Immunology, University of Gondar, Ethiopia.
authors.forename: Tekalign
authors.initials: T
authors.lastname: Deressa
authors.affiliation: Department of Immunology, University of Gondar, Ethiopia.
authors.forename: Biniam
authors.initials: B
authors.lastname: Mathewos
authors.affiliation: Department of Immunology, University of Gondar, Ethiopia.
authors.forename: Ebba
authors.initials: E
authors.lastname: Abate
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, United Kingdom.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Müller
authors.affiliation: Leishmaniasis Research and Treatment Centre, Gondar University, Ethiopia.|Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Yegnasew
authors.initials: Y
authors.lastname: Takele
authors.affiliation: Department of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Pascale
authors.initials: P
authors.lastname: Kropf
mesh_terms: D000293:Adolescent; D000328:Adult; D000953:Antigens, Protozoan / Q000276:immunology*; D001119:Arginase / Q000378:metabolism; D003430:Cross-Sectional Studies; D005002:Ethiopia; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D007194:India; D007371:Interferon-gamma / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy* / Q000473:pathology*; D008297:Male; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000953:Antigens, Protozoan; D016753:Interleukin-10; D007371:Interferon-gamma; D001119:Arginase