Human NK cells kill resting but not activated microglia via NKG2D- and NKp46-mediated recognition
| Autor: | Rosa Barreira da Silva, Anna Lünemann, Cedric S. Raine, Christian Münz, Jan D. Lünemann, Susanne Roberts, Brady Messmer |
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| Přispěvatelé: | University of Zurich, Münz, C |
| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Cytotoxicity
Immunologic Immunological Synapses NK Cell Lectin-Like Receptor Subfamily K Immunology 610 Medicine & health Cell Communication Lymphocyte Activation 10263 Institute of Experimental Immunology Resting Phase Cell Cycle Article Interleukin 21 Cell Movement MHC class I medicine Cell Adhesion Immunology and Allergy Cytotoxic T cell Humans Cells Cultured 2403 Immunology biology Microglia Cell Death Natural Cytotoxicity Triggering Receptor 1 Brain NKG2D Coculture Techniques Immunity Innate Cell biology Killer Cells Natural medicine.anatomical_structure Perforin Interleukin 12 biology.protein 2723 Immunology and Allergy 570 Life sciences |
| Zdroj: | Scopus-Elsevier |
| Popis: | Microglia are resident macrophage-like APCs of the CNS. To avoid escalation of inflammatory processes and bystander damage within the CNS, microglia-driven inflammatory responses need to be tightly regulated and both spatially and temporally restricted. Following traumatic, infectious, and autoimmune-mediated brain injury, NK cells have been found in the CNS, but the functional significance of NK cell recruitment and their mechanisms of action during brain inflammation are not well understood. In this study, we investigated whether and by which mechanisms human NK cells might edit resting and activated human microglial cells via killing in vitro. IL-2-activated NK cells efficiently killed both resting allogeneic and autologous microglia in a cell-contact-dependent manner. Activated NK cells rapidly formed synapses with human microglial cells in which perforin had been polarized to the cellular interface. Ab-mediated NKG2D and NKp46 blockade completely prevented the killing of human microglia by activated NK cells. Up-regulation of MHC class I surface expression by TLR4 stimulation protected microglia from NK cell-mediated killing, whereas MHC class I blockade enhanced cytotoxic NK cell activity. These data suggest that brain-infiltrating NK cells might restrict innate and adaptive immune responses within the human CNS via elimination of resting microglia. |
| Databáze: | OpenAIRE |
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