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NKp30-dependent cytolysis of filovirus-infected human dendritic cells.
- Source :
-
Cellular microbiology [Cell Microbiol] 2007 Apr; Vol. 9 (4), pp. 962-76. - Publication Year :
- 2007
-
Abstract
- Understanding how protective innate immune responses are generated is crucial to defeating highly lethal emerging pathogens. Accumulating evidence suggests that potent innate immune responses are tightly linked to control of Ebola and Marburg filoviral infections. Here, we report that unlike authentic or inactivated Ebola and Marburg, filovirus-derived virus-like particles directly activated human natural killer (NK) cells in vitro, evidenced by pro-inflammatory cytokine production and enhanced cytolysis of permissive target cells. Further, we observed perforin- and CD95L-mediated cytolysis of filovirus-infected human dendritic cells (DCs), primary targets of filovirus infection, by autologous NK cells. Gene expression knock-down studies directly linked NK cell lysis of infected DCs to upregulation of the natural cytotoxicity receptor, NKp30. These results are the first to propose a role for NK cells in the clearance of infected DCs and the potential involvement of NKp30-mediated cytolysis in control of viral infection in vivo. Further elucidation of the biology of NK cell activation, specifically natural cytotoxicity receptors like NKp30 and NKp46, promises to aid our understanding of microbial pathology.
- Subjects :
- Cell Death genetics
Cell Death physiology
Cells, Cultured
Cytokines metabolism
Cytotoxicity, Immunologic immunology
Dendritic Cells immunology
Dendritic Cells virology
Fas Ligand Protein metabolism
Flow Cytometry
Humans
K562 Cells
Killer Cells, Natural immunology
Killer Cells, Natural metabolism
Membrane Glycoproteins metabolism
Mutation
Natural Cytotoxicity Triggering Receptor 1
Natural Cytotoxicity Triggering Receptor 2
Natural Cytotoxicity Triggering Receptor 3
Perforin
Pore Forming Cytotoxic Proteins metabolism
Receptors, Immunologic genetics
Receptors, Immunologic metabolism
Virion growth & development
Dendritic Cells metabolism
Filoviridae growth & development
Receptors, Immunologic physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1462-5814
- Volume :
- 9
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cellular microbiology
- Publication Type :
- Academic Journal
- Accession number :
- 17381429
- Full Text :
- https://doi.org/10.1111/j.1462-5822.2006.00844.x