Syk kinase is required for collaborative cytokine production induced through Dectin-1 and Toll-like receptors.

European Journal of Immunology
Kevin M DennehyGordon D Brown

Abstract

Recognition of microbial components by germ-line encoded pattern recognition receptors (PRR) initiates immune responses to infectious agents. We and others have proposed that pairs or sets of PRR mediate host immunity. One such pair comprises the fungal beta-glucan receptor, Dectin-1, which collaborates through an undefined mechanism with Toll-like receptor 2 (TLR2) to induce optimal cytokine responses in macrophages. We show here that Dectin-1 signaling through the spleen tyrosine kinase (Syk) pathway is required for this collaboration, which can also occur with TLR4, 5, 7 and 9. Deficiency of either Syk or the TLR adaptor MyD88 abolished collaborative responses, which include TNF, MIP-1alpha and MIP-2 production, and which are comparable to the previously described synergy between TLR2 and TLR4. Collaboration of the Syk and TLR/MyD88 pathways results in sustained degradation of the inhibitor of kappaB (IkappaB), enhancing NFkappaB nuclear translocation. These findings establish the first example of Syk- and MyD88-coupled PRR collaboration, further supporting the concept that paired receptors collaborate to control infectious agents.

References

May 22, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J S Gerber, D M Mosser
Mar 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Joshua R BleharskiRobert L Modlin
Apr 30, 2003·The Journal of Experimental Medicine·Gordon D BrownSiamon Gordon
Apr 30, 2003·The Journal of Experimental Medicine·Benjamin N GantnerDavid M Underhill
Aug 12, 2004·Blood·Jurgen HerreGordon D Brown
Feb 4, 2005·Nature·Kasper HoebeBruce Beutler
May 17, 2005·Nature Immunology·Zhengfan JiangBruce Beutler
May 17, 2005·Nature Immunology·Jessica A HamermanLewis L Lanier
Sep 17, 2005·Science·Markus W CovertDavid Baltimore
Dec 13, 2005·Nature Reviews. Immunology·Gordon D Brown
Dec 14, 2005·Current Opinion in Immunology·Luke A J O'Neill
Jul 14, 2006·European Journal of Immunology·Andrew S J MarshallGordon D Brown
Aug 31, 2006·Journal of Virology·Chawaree ChaipanStefan Pöhlmann
Dec 13, 2006·Nature Immunology·Philip R TaylorGordon D Brown
Jan 5, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Aranya BagchiJudith Hellman
Feb 24, 2007·Nature Reviews. Immunology·Giorgio Trinchieri, Alan Sher
Apr 24, 2007·Nature Immunology·Salomé LeibundGut-LandmannCaetano Reis e Sousa
May 4, 2007·Journal of Leukocyte Biology·Kevin M Dennehy, Gordon D Brown

❮ Previous
Next ❯

Citations

Aug 12, 2010·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Mohlopheni J MarakalalaGordon D Brown
May 12, 2011·Pharmaceutical Research·Samar HamdyAfsaneh Lavasanifar
Aug 6, 2008·Immunology and Cell Biology·Sandra J van VlietYvette van Kooyk
Aug 23, 2012·Nature Immunology·Sarah E Hardison, Gordon D Brown
Sep 19, 2008·Nature Immunology·Gordon D Brown
Jun 2, 2009·Nature Reviews. Drug Discovery·Matthias GaestelMichael Kracht
Oct 30, 2009·The New England Journal of Medicine·Bart FerwerdaMihai G Netea
Jan 7, 2011·The New England Journal of Medicine·Mihai G Netea, Jos W M van der Meer
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Simona GalloriniAndreas Wack
Jan 6, 2011·The Journal of Biological Chemistry·Umut GaziLuisa Martinez-Pomares
Apr 15, 2008·The Journal of Biological Chemistry·Cristal HuysamenGordon D Brown
Jul 9, 2008·Medical Mycology·Matti Kimberg, Gordon D Brown
May 31, 2011·Journal of Toxicology and Environmental Health. Part a·Edilson R Alves-FilhoJane L Dos Santos
Mar 2, 2011·Infection and Immunity·Héctor M Mora-MontesNeil A R Gow
Feb 7, 2013·MBio·Suganya ViriyakosolJoshua Fierer
Dec 2, 2010·Microbiology and Molecular Biology Reviews : MMBR·Elizabeth A MischThomas R Hawn
Jul 19, 2012·Biochemistry. Biokhimii︠a︡·Y Sh Schwartz, A V Svistelnik
Jun 9, 2009·American Journal of Respiratory Cell and Molecular Biology·Rajinder P PartiChristina C Leslie
Feb 22, 2012·American Journal of Respiratory Cell and Molecular Biology·Eva M CarmonaAndrew H Limper
Feb 18, 2010·Arthritis Research & Therapy·Theo S PlantingaLeo Ab Joosten
Jul 31, 2012·Arthritis Research & Therapy·Anna R HupplerSarah L Gaffen
Mar 18, 2009·Journal of Leukocyte Biology·Michelle H W LairdStefanie N Vogel
Aug 13, 2013·PLoS Neglected Tropical Diseases·João Filipe MeninoFernando Rodrigues
Apr 27, 2012·PloS One·Inês Faro-TrindadeGordon D Brown
May 3, 2013·PloS One·Cristina MunicioMariano Sánchez Crespo
Mar 4, 2014·PLoS Pathogens·Makoto Inoue, Mari L Shinohara
Jan 29, 2011·Clinical & Developmental Immunology·Mohlopheni Jackson MarakalalaGordon D Brown
Apr 12, 2014·Cellular Immunology·Linda M van den BergTeunis B H Geijtenbeek
Sep 26, 2013·BioMed Research International·Mónica I Villaseñor-CardosoEnrique Ortega
Apr 30, 2013·International Immunopharmacology·Huimin YanNoriko M Tsuji
Jan 10, 2012·Annual Review of Immunology·Marcel WüthrichBruce Klein
Aug 12, 2014·International Journal of Microbiology·Iván Martínez-DunckerHéctor M Mora-Montes
Sep 21, 2010·Biochemical and Biophysical Research Communications·Morihiko Nakamura, Natsuko Watanabe

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear translocation
fluorescence microscopy
FCS
ELISA

Related Concepts

Related Feeds

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.