Synergistic activation of dendritic cells by combined Toll-like receptor ligation induces superior CTL responses in vivo

Blood
Tobias WargerMarkus P Radsak

Abstract

Toll-like receptors (TLRs) are able to interact with pathogen-derived products and their signals induce the coordinated activation of innate and adaptive immune mechanisms. Dendritic cells (DCs) play a central role in these events. As the different TLRs are able to trigger MyD88/TRIF-dependent and -independent signaling pathways, we wondered if the simultaneous activation of these signaling cascades would synergize with respect to DC activation and induce superior cytotoxic T-lymphocyte (CTL) activity in vivo. We observed that indeed the combined activation of MyD88-dependent and -independent signaling induced by TLR7 and TLR3 ligands provoked a more rapid and more sustained bone marrow-derived DC (BMDC) activation with regard to the secretion of proinflammatory cytokines, like IL-6 and IL-12p70, and the expression of costimulatory molecules like CD40, CD70, and CD86. Furthermore, in the presence of combined TLR ligand-stimulated DCs, CD4(+) and CD8(+) T cells were insensitive toward the inhibitory effects of regulatory T cells. Most importantly, peptide-loaded BMDCs stimulated by TLR ligand combinations resulted in a marked increase of CTL effector functions in wild-type mice in vivo. Thus, our results provide evidence that un...Continue Reading

References

Jan 1, 1994·Annual Review of Immunology·T BoonA Van Pel
Jan 1, 1993·Annual Review of Immunology·F W FitchT F Gajewski
Apr 1, 1998·Nature·J Banchereau, R M Steinman
Aug 6, 1999·Immunity·T KawaiS Akira
Aug 30, 2001·Nature Immunology·T HorngR Medzhitov
Sep 8, 2001·Nature Immunology·M SchnareR Medzhitov
Mar 6, 2002·The Journal of Experimental Medicine·Albert Bendelac, Ruslan Medzhitov
Mar 22, 2002·Nature Reviews. Immunology·R Medzhitov
Mar 26, 2002·The Journal of Biological Chemistry·Ramunas M VabulasHansjorg Schild
Apr 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryan A WilcoxLieping Chen
Aug 30, 2002·Trends in Immunology·Manfred B Lutz, Gerold Schuler
Dec 10, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Masahiro YamamotoShizuo Akira
Jan 18, 2003·Science·Chandrashekhar Pasare, Ruslan Medzhitov
Apr 15, 2003·Nature Immunology·Katherine A FitzgeraldTom Maniatis
Jun 5, 2003·European Journal of Immunology·Katrin SchwarzMartin F Bachmann
Apr 17, 2004·British Journal of Haematology·Sibylla BraedelHolger Hebart
May 4, 2004·Nature Medicine·Carl G FigdorCornelis J M Melief
Jun 9, 2004·The Journal of Experimental Medicine·Ramon ArensMarinus H J van Oers
Jun 24, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael StassenEdgar Schmitt
Sep 30, 2004·Nature Immunology·Akiko Iwasaki, Ruslan Medzhitov
Nov 13, 2004·Immunity·Chandrashekhar Pasare, Ruslan Medzhitov
Jan 7, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Timothy N J Bullock, Hideo Yagita
Feb 25, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gerd RechtsteinerMarkus P Radsak

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Citations

Oct 28, 2008·Cancer Immunology, Immunotherapy : CII·Cornelia WurzenbergerCarole Bourquin
Feb 3, 2009·Cancer Immunology, Immunotherapy : CII·Tsukasa Seya, Misako Matsumoto
Apr 3, 2010·Cancer Immunology, Immunotherapy : CII·Tobias BoppHansjörg Schild
Sep 22, 2010·Pflügers Archiv : European journal of physiology·Anand RotteFlorian Lang
May 23, 2006·Medical Microbiology and Immunology·Christian BeckerHelmut Jonuleit
Feb 24, 2007·Nature Reviews. Immunology·Giorgio Trinchieri, Alan Sher
Feb 28, 2013·Integrative Biology : Quantitative Biosciences From Nano to Macro·Jose L Garcia-CorderoSebastian J Maerkl
Oct 11, 2008·Proceedings of the National Academy of Sciences of the United States of America·Qing ZhuJay A Berzofsky
May 20, 2009·The Journal of Experimental Medicine·Ryutaro FukuiKensuke Miyake
Mar 20, 2010·Journal of Virology·Karine BreckpotMary Collins
Nov 6, 2007·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Ekaterina ShumilinaFlorian Lang
May 4, 2007·The Journal of Clinical Investigation·Eli Gilboa
Dec 22, 2009·Journal of Translational Medicine·Sébastien AnguilleVigor F I Van Tendeloo
Jan 3, 2012·Journal of Translational Medicine·Jitka FučíkováRadek Špíšek
Apr 18, 2013·PLoS Neglected Tropical Diseases·Xuefeng WangChuan Su
Aug 3, 2012·Immunotherapy·Arpit BhargavaPradyumna Kumar Mishra
May 18, 2010·Immunotherapy·Rachel Lubong Sabado, Nina Bhardwaj
Oct 10, 2013·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Natarajan AyithanKeiko Ozato
Jul 31, 2012·Therapeutic Delivery·Yoshio Fujita, Hiroaki Taguchi
Mar 12, 2013·Journal of Leukocyte Biology·Sabina KaczanowskaEduardo Davila
Sep 10, 2014·Expert Review of Vaccines·Daphné BenteynKarine Breckpot
Aug 3, 2007·Expert Review of Vaccines·Martijn S BijkerSjoerd H van der Burg
Aug 3, 2007·Expert Review of Vaccines·Cara K FraserJohn D Hayball
Oct 13, 2007·Expert Review of Vaccines·Mark A TomaiJohn P Vasilakos
Sep 1, 2009·Expert Review of Clinical Pharmacology·Anupama Sharma, Brian J Czerniecki
Dec 5, 2012·Expert Opinion on Investigational Drugs·Thomas MeyerEggert Stockfleth
Aug 19, 2007·Annals of Medicine·Tobias BoppEdgar Schmitt

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