NKp30-dependent cytolysis of filovirus-infected human dendritic cells.
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.
Fuller
Claudette L
CL
United States Army Medical Research Institute of Infectious Diseases, Frederick, MD 21702, USA.
Ruthel
Gordon
G
Warfield
Kelly L
KL
Swenson
Dana L
DL
Bosio
Catharine M
CM
Aman
M Javad
MJ
Bavari
Sina
S
D016923:Cell Death / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D053222:Fas Ligand Protein / Q000378:metabolism; D016563:Filoviridae / Q000254:growth & development*; D005434:Flow Cytometry; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009154:Mutation; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D055628:Natural Cytotoxicity Triggering Receptor 3; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014771:Virion / Q000254:growth & development
D016207:Cytokines; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; C112260:NCR1 protein, human; C112837:NCR2 protein, human; C431710:NCR3 protein, human; D055627:Natural Cytotoxicity Triggering Receptor 1; D055629:Natural Cytotoxicity Triggering Receptor 2; D055628:Natural Cytotoxicity Triggering Receptor 3; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic; D054353:Perforin