title: The interplay between Leishmania promastigotes and human Natural Killer cells in vitro leads to direct lysis of Leishmania by NK cells and modulation of NK cell activity by Leishmania promastigotes.
abstract: NK cells represent one of the first lines of defence in the immune reaction after invasion of Leishmania parasites. Depletion of mouse natural killer (NK) cells dramatically enhances susceptibility of normally resistant mice. In this study we evaluated the fate of NK cells and parasites after contact formation. The hydrophilic fluorescent dye CMFDA (chloro-methylfluorescin diacetate) that allows analysis of cytotoxicity in flow cytometry and microscopy was used. Furthermore, these findings were confirmed with scanning and transmission electron microscopy. Direct contact points were found between Leishmania promastigotes and naïve human NK cells. These contacts were associated with transfer of cytosol by membrane bridges and cytotoxicity of NK cells against Leishmania. However, in contrast to other target cells which allow repeated exocytosis of lytic granules, contact with Leishmania causes immediate destruction of NK cells in a non-apoptotic way. Our results give a reasonable explanation for ex vivo observations of reduced NK cell numbers and impaired NK response in patients with acute cutaneous leishmaniasis. Animal models have clearly shown that NK cells play a key role in the induction and direction of the immune response. Thus inhibition of NK cells at the onset of infection would be advantageous for the survival of the parasite.
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177 Stockholm, Sweden.
authors: Thorsten
authors: T
authors: Lieke
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177 Stockholm, Sweden.
authors: Susanne
authors: S
authors: Nylén
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177 Stockholm, Sweden.
authors: Liv
authors: L
authors: Eidsmo
authors: Bernhard Nocht Institute for Tropical Medicine, Parasitology Section, Bernhard Nocht Strasse 74, 20359 Hamburg, Germany.
authors: Christel
authors: C
authors: Schmetz
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177 Stockholm, Sweden.
authors: Louise
authors: L
authors: Berg
authors: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Nobels väg 16, 17177 Stockholm, Sweden.
authors: Hannah
authors: H
authors: Akuffo
mesh_terms: D016923:Cell Death / Q000276:immunology; D005434:Flow Cytometry; D005452:Fluoresceins; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology*; D007891:Leishmania / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology; D008213:Lymphocyte Activation
chemical_list: D005452:Fluoresceins; C069306:5-chloromethylfluorescein