Distinct roles of TLR2 and the adaptor ASC in IL-1beta/IL-18 secretion in response to Listeria monocytogenes - PubMed (original) (raw)

. 2006 Apr 1;176(7):4337-42.

doi: 10.4049/jimmunol.176.7.4337.

Junya Masumoto, Luigi Franchi, Thirumala-Devi Kanneganti, Mathilde Body-Malapel, Ilkim Ertürk, Rajesh Jagirdar, Li Zhu, Naohiro Inohara, John Bertin, Anthony Coyle, Ethan P Grant, Gabriel Núñez

Affiliations

Distinct roles of TLR2 and the adaptor ASC in IL-1beta/IL-18 secretion in response to Listeria monocytogenes

Nesrin Ozören et al. J Immunol. 2006.

Abstract

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-1beta/IL-18, but dispensable for IL-6, TNF-alpha, and IFN-beta production, in macrophages infected with Listeria. Activation of caspase-1 was abolished in ASC-deficient macrophages, whereas activation of NF-kappaB and p38 was unaffected. In contrast, secretion of IL-1beta, IL-6, and TNF-alpha was reduced in TLR2-deficient macrophages infected with Listeria; this was associated with impaired activation of NF-kappaB and p38, but normal caspase-1 processing. Analysis of Listeria mutants revealed that cytosolic invasion was required for ASC-dependent IL-1beta secretion, consistent with a critical role for cytosolic signaling in the activation of caspase-1. Secretion of IL-1beta 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-1beta via distinct mechanisms in response to Listeria. ASC, but not TLR2, is required for caspase-1 activation independent of NF-kappaB in Listeria-infected macrophages.

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