APC-independent activation of NK cells by the Toll-like receptor 3 agonist double-stranded RNA.
Toll-like receptors (TLRs) play a fundamental role in the recognition of bacteria and viruses. TLR3 is activated by viral dsRNA and polyinosinic-polycytidylic acid (poly(I:C)), a synthetic mimetic of viral RNA. We show that NK cells, known for their capacity to eliminate virally infected cells, express TLR3 and up-regulate TLR3 mRNA upon poly(I:C) stimulation. Treatment of highly purified NK cells with poly(I:C) significantly augments NK cell-mediated cytotoxicity. Poly(I:C) stimulation also leads to up-regulation of activation marker CD69 on NK cells. Furthermore, NK cells respond to poly(I:C) by producing proinflammatory cytokines like IL-6 and IL-8, as well as the antiviral cytokine IFN-gamma. The induction of cytokine production by NK cells was preceded by activation of NF-kappaB. We conclude that the ability of NK cells to directly recognize and respond to viral products is important in mounting effective antiviral responses.
Schmidt
Kerstin N
KN
Department of Immunology, Genentech, Inc., MS #63, One DNA Way, South San Francisco, CA 94080, USA. kerstin@gene.com
Leung
Beatrice
B
Kwong
Mandy
M
Zarember
Kol A
KA
Satyal
Sanjeev
S
Navas
Tony A
TA
Wang
Fay
F
Godowski
Paul J
PJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis / Q000502:physiology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008562:Membrane Glycoproteins / Q000819:agonists* / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D011070:Poly I-C / Q000494:pharmacology; D012330:RNA, Double-Stranded / Q000494:pharmacology / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000096:biosynthesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology; D000099192:CD69 Antigens
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D016207:Cytokines; D007370:Interferon Type I; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011070:Poly I-C; D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D051196:Toll-Like Receptor 3; D051193:Toll-Like Receptors; D000099192:CD69 Antigens; C495344:TLR3 protein, human