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TLR3 and Rig-Like Receptor on Myeloid Dendritic Cells and Rig-Like Receptor on Human NK Cells Are Both Mandatory for Production of IFN-gamma in Response to Double-Stranded RNA

  1. Author:
    Perrot, I.
    Deauvieau, F.
    Massacrier, C.
    Hughes, N.
    Garrone, P.
    Durand, I.
    Demaria, O.
    Viaud, N.
    Gauthier, L.
    Blery, M.
    Bonnefoy-Berard, N.
    Morel, Y.
    Tschopp, J.
    Alexopoulou, L.
    Trinchieri, G.
    Paturel, C.
    Caux, C.

  2. Author Address

    [Deauvieau, Florence; Durand, Isabelle; Caux, Christophe] Ctr Leon Berard, Inst Natl Sante, Equipe Cyto Kines & Canc, Rech Med Unite 590, F-69373 Lyon, France. [Demaria, Olivier; Alexopoulou, Lena] Ctr Immunol Marseille Luminy, Marseille, France. [Demaria, Olivier; Alexopoulou, Lena] Innate Pharma, Marseille, France. [Bonnefoy-Berard, Nathalie] Inst Natl Sante, Rech Med Unite 851, Lyon, France. [Tschopp, Jurg] Univ Lausanne, Dept Biochem, CH-1066 Epalinges, Switzerland. [Paturel, Carine] NCI, Canc & Inflammat Program, Ctr Canc Res, Frederick, MD 21702 USA. [Deauvieau, Florence; Durand, Isabelle; Caux, Christophe] Epixis, Lyon, France.;Caux, C, Ctr Leon Berard, Inst Natl Sante, Equipe Cyto Kines & Canc, Rech Med Unite 590, 28 Rue Laennec, F-69373 Lyon, France.;cauxc@lyon.fnclcc.fr
    1. Year: 2010
    2. Date: Aug
  2. Journal: Journal of Immunology
    1. 185
    2. 4
    3. Pages: 2080-2088
  4. Type of Article: Article
  5. ISSN: 0022-1767
  1. Abstract:

    Cross-talk between NK cells and dendritic cells (DCs) is critical for the potent therapeutic response to dsRNA, but the receptors involved remained controversial. We show in this paper that two dsRNAs, polyadenylic-polyuridylic acid and polyinosinic-polycytidylic acid [poly(I: C)], similarly engaged human TLR3, whereas only poly(I:C) triggered human RIG-I and MDA5. Both dsRNA enhanced NK cell activation within PBMCs but only poly(I:C) induced IFN-gamma. Although myeloid DCs (mDCs) were required for NK cell activation, induction of cytolytic potential and IFN-gamma production did not require contact with mDCs but was dependent on type I IFN and IL-12, respectively. Poly(I:C) but not polyadenylic-polyuridylic acid synergized with mDC-derived IL-12 for IFN-gamma production by acting directly on NK cells. Finally, the requirement of both TLR3 and Rig-like receptor (RLR) on mDCs and RLRs but not TLR3 on NK cells for IFN-gamma production was demonstrated using TLR3- and Cardif-deficient mice and human RIG-I-specific activator. Thus, we report the requirement of cotriggering TLR3 and RLR on mDCs and RLRs on NK cells for a pathogen product to induce potent innate cell activation. The Journal of Immunology, 2010, 185: 2080-2088.

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External Sources

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  2. DOI: 10.4049/jimmunol.1000532
  3. View record in Web of Science®
  4. WOS: 000280661900014

Library Notes

  1. Fiscal Year: FY2009-2010
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