HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Özören, N. Articles by Núñez, G. Search for Related Content PubMed PubMed Citation Articles by Özören, N. Articles by Núñez, G.

Distinct Roles of TLR2 and the Adaptor ASC in IL-1/IL-18 Secretion in Response to Listeria monocytogenes¹

Nesrin Özören^2,*, Junya Masumoto^3,*, Luigi Franchi^*, Thirumala-Devi Kanneganti^*, Mathilde Body-Malapel^*, lkim Ertürk^*, Rajesh Jagirdar^*, Li Zhu^*, Naohiro Inohara^*, John Bertin^4,, Anthony Coyle^5,, Ethan P. Grant^4, and Gabriel Núñez^6,*

^* Department of Pathology and Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI 48109; and Millennium Pharmaceuticals, Inc., Cambridge, MA 02139

Apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) is an adaptor molecule that has recently been implicated in the activation of caspase-1. We have studied the role of ASC in the host defense against the intracellular pathogen Listeria monocytogenes. ASC was found to be essential for the secretion of IL-1/IL-18, but dispensable for IL-6, TNF-, and IFN- production, in macrophages infected with Listeria. Activation of caspase-1 was abolished in ASC-deficient macrophages, whereas activation of NF-B and p38 was unaffected. In contrast, secretion of IL-1, IL-6, and TNF- was reduced in TLR2-deficient macrophages infected with Listeria; this was associated with impaired activation of NF-B and p38, but normal caspase-1 processing. Analysis of Listeria mutants revealed that cytosolic invasion was required for ASC-dependent IL-1 secretion, consistent with a critical role for cytosolic signaling in the activation of caspase-1. Secretion of IL-1 in response to lipopeptide, a TLR2 agonist, was greatly reduced in ASC-null macrophages and was abolished in TLR2-deficient macrophages. These results demonstrate that TLR2 and ASC regulate the secretion of IL-1 via distinct mechanisms in response to Listeria. ASC, but not TLR2, is required for caspase-1 activation independent of NF-B in Listeria-infected macrophages.

This article has been cited by other articles:

				N. Gratz, M. Siller, B. Schaljo, Z. A. Pirzada, I. Gattermeier, I. Vojtek, C. J. Kirschning, H. Wagner, S. Akira, E. Charpentier, et al. Group A Streptococcus Activates Type I Interferon Production and MyD88-dependent Signaling without Involvement of TLR2, TLR4, and TLR9 J. Biol. Chem., July 18, 2008; 283(29): 19879 - 19887. [Abstract] [Full Text] [PDF]

				H. Hara, K. Tsuchiya, T. Nomura, I. Kawamura, S. Shoma, and M. Mitsuyama Dependency of Caspase-1 Activation Induced in Macrophages by Listeria monocytogenes on Cytolysin, Listeriolysin O, after Evasion from Phagosome into the Cytoplasm J. Immunol., June 15, 2008; 180(12): 7859 - 7868. [Abstract] [Full Text] [PDF]

				J. P. de Rivero Vaccari, G. Lotocki, A. E. Marcillo, W. D. Dietrich, and R. W. Keane A Molecular Platform in Neurons Regulates Inflammation after Spinal Cord Injury J. Neurosci., March 26, 2008; 28(13): 3404 - 3414. [Abstract] [Full Text] [PDF]

				H. Zwaferink, S. Stockinger, P. Hazemi, R. Lemmens-Gruber, and T. Decker IFN-{beta} Increases Listeriolysin O-Induced Membrane Permeabilization and Death of Macrophages J. Immunol., March 15, 2008; 180(6): 4116 - 4123. [Abstract] [Full Text] [PDF]

				K. Yamauchi, I.-J. Choi, H. Lu, H. Ogiwara, D. Y. Graham, and Y. Yamaoka Regulation of IL-18 in Helicobacter pylori Infection J. Immunol., January 15, 2008; 180(2): 1207 - 1216. [Abstract] [Full Text] [PDF]

				C. Stehlik and A. Dorfleutner COPs and POPs: Modulators of Inflammasome Activity J. Immunol., December 15, 2007; 179(12): 7993 - 7998. [Abstract] [Full Text] [PDF]

				K. Yoshimura, L. S. Laird, C. Y. Chia, K. F. Meckel, J. E. Slansky, J. M. Thompson, A. Jain, D. M. Pardoll, and R. D. Schulick Live Attenuated Listeria Monocytogenes Effectively Treats Hepatic Colorectal Cancer Metastases and Is Strongly Enhanced by Depletion of Regulatory T Cells Cancer Res., October 15, 2007; 67(20): 10058 - 10066. [Abstract] [Full Text] [PDF]

				M. Lamkanfi, T.-D. Kanneganti, L. Franchi, and G. Nunez Caspase-1 inflammasomes in infection and inflammation J. Leukoc. Biol., August 1, 2007; 82(2): 220 - 225. [Abstract] [Full Text] [PDF]

				J.-H. Park, Y.-G. Kim, M. Shaw, T.-D. Kanneganti, Y. Fujimoto, K. Fukase, N. Inohara, and G. Nunez Nod1/RICK and TLR Signaling Regulate Chemokine and Antimicrobial Innate Immune Responses in Mesothelial Cells J. Immunol., July 1, 2007; 179(1): 514 - 521. [Abstract] [Full Text] [PDF]

				L. Franchi, T.-D. Kanneganti, G. R. Dubyak, and G. Nunez Differential Requirement of P2X7 Receptor and Intracellular K+ for Caspase-1 Activation Induced by Intracellular and Extracellular Bacteria J. Biol. Chem., June 29, 2007; 282(26): 18810 - 18818. [Abstract] [Full Text] [PDF]

				D. S. WEISS, T. HENRY, and D. M. MONACK Francisella Tularensis: Activation of the Inflammasome Ann. N.Y. Acad. Sci., June 1, 2007; 1105(1): 219 - 237. [Abstract] [Full Text] [PDF]

				S. Basu, T. J. Kang, W. H. Chen, M. J. Fenton, L. Baillie, S. Hibbs, and A. S. Cross Role of Bacillus anthracis Spore Structures in Macrophage Cytokine Responses Infect. Immun., May 1, 2007; 75(5): 2351 - 2358. [Abstract] [Full Text] [PDF]

				M. W. Moore, A. R. Cruz, C. J. LaVake, A. L. Marzo, C. H. Eggers, J. C. Salazar, and J. D. Radolf Phagocytosis of Borrelia burgdorferi and Treponema pallidum Potentiates Innate Immune Activation and Induces Gamma Interferon Production Infect. Immun., April 1, 2007; 75(4): 2046 - 2062. [Abstract] [Full Text] [PDF]

				J.-H. Park, Y.-G. Kim, C. McDonald, T.-D. Kanneganti, M. Hasegawa, M. Body-Malapel, N. Inohara, and G. Nunez RICK/RIP2 Mediates Innate Immune Responses Induced through Nod1 and Nod2 but Not TLRs J. Immunol., February 15, 2007; 178(4): 2380 - 2386. [Abstract] [Full Text] [PDF]

				T.-D. Kanneganti, M. Body-Malapel, A. Amer, J.-H. Park, J. Whitfield, L. Franchi, Z. F. Taraporewala, D. Miller, J. T. Patton, N. Inohara, et al. Critical Role for Cryopyrin/Nalp3 in Activation of Caspase-1 in Response to Viral Infection and Double-stranded RNA J. Biol. Chem., December 1, 2006; 281(48): 36560 - 36568. [Abstract] [Full Text] [PDF]

				D. J. Taxman, J. Zhang, C. Champagne, D. T. Bergstralh, H. A. Iocca, J. D. Lich, and J. P.-Y. Ting Cutting Edge: ASC Mediates the Induction of Multiple Cytokines by Porphyromonas gingivalis via Caspase-1-Dependent and -Independent Pathways J. Immunol., October 1, 2006; 177(7): 4252 - 4256. [Abstract] [Full Text] [PDF]

				L. Franchi, C. McDonald, T.-D. Kanneganti, A. Amer, and G. Nunez Nucleotide-Binding Oligomerization Domain-Like Receptors: Intracellular Pattern Recognition Molecules for Pathogen Detection and Host Defense J. Immunol., September 15, 2006; 177(6): 3507 - 3513. [Abstract] [Full Text] [PDF]