MBE Advance Access published online on December 26, 2006
Molecular Biology and Evolution, doi:10.1093/molbev/msl208
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Research Article |
Toll-Like Receptors are Part of the Innate Immune Defense System of Sponges (Demospongiae: Porifera)
-OttstadtInstitut für Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Universität, Duesbergweg 6, D-55099 Mainz; GERMANY
Correspondence to: Dr. M. Wiens; Institut für Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Universität, Duesbergweg 6, 55099 Mainz; GERMANY; tel.: +49-6131-392-5961; fax.: +49-6131-392-5243. e-mail: wiens{at}uni-mainz.de
Accepted for publication December 18, 2006.
During evolution and with the emergence of multicellular animals the need arose to ward off foreign organisms that threaten the integrity of the animal body. Among many different receptors that participate in the recognition of microbial invaders, Toll-like receptors (TLRs) play an essential role in mediating the innate immune response. After binding distinct microbial components TLRs activate intracellular signaling cascades that result in an induced expression of diverse antimicrobial molecules. Since sponges [phylum Porifera] are filter feeders, they are abundantly exposed to microorganisms that represent a potential threat. Here we describe the identification, cloning and deduced protein sequence from three major elements of the poriferan innate response (to bacterial lipopeptides): the Toll-like receptor, the protein kinase IRAK4l, and a novel effector caspase from the demosponge Suberites domuncula. Each molecule shares significant sequence similarity with its homologues in higher Metazoa. Sequence homologies were found in particular within the family specific domains TIR (TLR family), STYKc (IRAK family), and CASc (caspase family). In addition, in situ hybridization and immunohistological analyses revealed an abundance of SDTLR (Toll-like receptor) transcripts in epithelial layers of the sponge surface (exopinacoderm and endopinacoderm). Furthermore, it is shown that both, SDTLR and SDIRAK4-like (IRAK) are expressed constitutively, regardless of treatment with synthetic triacyl lipopeptide Pam3Cys-Ser-(Lys)4. In contrast, SDCASL (caspase) expression is highly Pam3Cys-Ser-(Lys)4-inducible. However, blocking of the lipopeptide with recombinant TLR prior to its application completely prevented the induced expression of this poriferan caspase. These results underscore that the phylogenetically oldest extant metazoan phylum is provided already with the signaling pathways of the anti-microbial host-defense system of Metazoa.
Key Words: Sponges innate immunity Toll-like receptor IRAK TIR death domain caspase lipoproteins
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