title: Innate immune defense of the sponge Suberites domuncula against bacteria involves a MyD88-dependent signaling pathway. Induction of a perforin-like molecule.
abstract: Sponges (phylum Porifera) are the phylogenetically oldest metazoa; as filter feeders, they are abundantly exposed to marine microorganisms. Here we present data indicating that the demosponge Suberites domuncula is provided with a recognition system for gram-negative bacteria. The lipopolysaccharide (LPS)-interacting protein was identified as a receptor on the sponge cell surface, which recognizes the bacterial endotoxin LPS. The cDNA was isolated, and the protein (Mr 49,937) was expressed. During binding to LPS, the protein dimerizes and interacts with MyD88, which was also identified and cloned. The sponge MyD88 (Mr 28,441) is composed of two protein interaction domains, a Toll/interleukin-1 receptor domain (found in MyD88 and in Toll-like receptors) and a death domain (present in MyD88 and interleukin-1 receptor-associated kinase). Northern blot experiments and in situ hybridization studies showed that after LPS treatment, the level of the LPS-interacting protein remains unchanged, whereas MyD88 is strongly up-regulated. A perforin-like molecule (Mr 74,171), the macrophage-expressed protein, was identified as an executing molecule of this pathway. This gene is highly expressed after LPS treatment, especially at the surfaces of the animals. The recombinant protein possesses biological activity and eliminates gram-negative bacteria; it is inactive against gram-positive bacteria. These data indicate that S. domuncula is provided with an innate immune system against gram-negative bacteria; the ligand LPS (a pathogen-associated molecular pattern) is recognized by the pattern recognition receptor (LPS-interacting protein), which interacts with MyD88. A signal transduction is established, which results in an elevated expression of MyD88 as well as of the macrophage-expressed protein as an executing protein.
authors.affiliation: Institut für Physiologische Chemie, Abteilung Angewandte Molekularbiologie, Universität, Duesbergweg 6, D-55099 Mainz, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Wiens
authors.forename: Michael
authors.initials: M
authors.lastname: Korzhev
authors.forename: Anatoli
authors.initials: A
authors.lastname: Krasko
authors.forename: Narsinh L
authors.initials: NL
authors.lastname: Thakur
authors.forename: Sanja
authors.initials: S
authors.lastname: Perović-Ottstadt
authors.forename: Hans J
authors.initials: HJ
authors.lastname: Breter
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ushijima
authors.forename: Bärbel
authors.initials: B
authors.lastname: Diehl-Seifert
authors.forename: Isabel M
authors.initials: IM
authors.lastname: Müller
authors.forename: Werner E G
authors.initials: WE
authors.lastname: Müller
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D000943:Antigens, Differentiation / Q000737:chemistry*; D015152:Blotting, Northern; D015153:Blotting, Western; D003001:Cloning, Molecular; D003432:Cross-Linking Reagents / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D019281:Dimerization; D016650:Fluorescein-5-isothiocyanate / Q000494:pharmacology; D015723:Gene Library; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D017403:In Situ Hybridization; D008024:Ligands; D008070:Lipopolysaccharides / Q000737:chemistry; D008264:Macrophages / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000737:chemistry*; D008954:Models, Biological; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D054353:Perforin; D010802:Phylogeny; D052899:Pore Forming Cytotoxic Proteins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012313:RNA / Q000737:chemistry; D011971:Receptors, Immunologic / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D047233:Suberites / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D003432:Cross-Linking Reagents; D018076:DNA, Complementary; D008024:Ligands; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D052899:Pore Forming Cytotoxic Proteins; D011971:Receptors, Immunologic; D011994:Recombinant Proteins; D054353:Perforin; D012313:RNA; D016650:Fluorescein-5-isothiocyanate