Uncovering the evolutionary history of innate immunity: the simple metazoan Hydra uses epithelial cells for host defence.

Although many properties of the innate immune system are shared among multicellular animals, the evolutionary origin remains poorly understood. Here we characterize the innate immune system in Hydra, one of the simplest multicellular animals known. In the complete absence of both protective mechanical barriers and mobile phagocytes, Hydra's epithelium is remarkably well equipped with potent antimicrobial peptides to prevent pathogen infection. Induction of antimicrobial peptide production is mediated by the interaction of a leucine-rich repeats (LRRs) domain containing protein with a TIR-domain containing protein lacking LRRs. Conventional Toll-like receptors (TLRs) are absent in the Hydra genome. Our findings support the hypothesis that the epithelium represents the ancient system of host defence.

[1]  Peer Bork,et al.  SMART 4.0: towards genomic data integration , 2004, Nucleic Acids Res..

[2]  T. Bosch,et al.  Role of epithelial cells and programmed cell death in Hydra spermatogenesis. , 2001, Zoology.

[3]  J. Rast,et al.  Genomic Insights into the Immune System of the Sea Urchin , 2006, Science.

[4]  J. Schröder,et al.  Isolation and Characterization of Human β-Defensin-3, a Novel Human Inducible Peptide Antibiotic* , 2001, The Journal of Biological Chemistry.

[5]  John Quackenbush,et al.  TIGR Gene Indices clustering tools (TGICL): a software system for fast clustering of large EST datasets , 2003, Bioinform..

[6]  Sudhir Kumar,et al.  MEGA3: Integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment , 2004, Briefings Bioinform..

[7]  M. Zasloff,et al.  The nervous system and innate immunity: the neuropeptide connection. , 2005, Nature immunology.

[8]  M. Gale,et al.  CARD games between virus and host get a new player. , 2006, Trends in immunology.

[9]  J. Schröder,et al.  Burkholderia Is Highly Resistant to Human Beta-Defensin 3 , 2003, Antimicrobial Agents and Chemotherapy.

[10]  J. Schröder,et al.  Antimicrobial psoriasin (S100A7) protects human skin from Escherichia coli infection , 2005, Nature Immunology.

[11]  C. David,et al.  Immunocompetence in Hydra. Epithelial cells recognize self-nonself and react against it , 1986 .

[12]  J. Lohmann,et al.  Transgenic Hydra allow in vivo tracking of individual stem cells during morphogenesis. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[13]  Charles A. Janeway,et al.  Decoding the Patterns of Self and Nonself by the Innate Immune System , 2002, Science.

[14]  Nektarios Tavernarakis,et al.  Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection , 2007, Genome Biology.

[15]  B. Lemaître,et al.  Pathogen Surveillance--the Flies Have It , 2002, Science.

[16]  P. Matzinger.  The Danger Model: A Renewed Sense of Self , 2002, Science.

[17]  J. Schröder.  Identification and structural characterization of chemokines in lesional skin material of patients with inflammatory skin disease. , 1997, Methods in enzymology.

[18]  S. Akira,et al.  Pathogen Recognition and Innate Immunity , 2006, Cell.

[19]  John P. Cannon,et al.  Reconstructing immune phylogeny: new perspectives , 2005, Nature Reviews Immunology.

[20]  T. Bosch,et al.  Long-term maintenance of species-specific bacterial microbiota in the basal metazoan Hydra , 2007, Proceedings of the National Academy of Sciences.

[21]  J. Lohmann,et al.  Silencing of developmental genes in Hydra. , 1999, Developmental biology.

[22]  P. Sautière,et al.  Molecular Characterization of Two Novel Antibacterial Peptides Inducible upon Bacterial Challenge in an Annelid, the Leech Theromyzon tessulatum* , 2004, Journal of Biological Chemistry.

[23]  Mario Albrecht,et al.  Genetics of Crohn disease, an archetypal inflammatory barrier disease , 2005, Nature Reviews Genetics.

[24]  Sean R. Eddy,et al.  Profile hidden Markov models , 1998, Bioinform..

[25]  Thomas C G Bosch,et al.  Why polyps regenerate and we don't: towards a cellular and molecular framework for Hydra regeneration. , 2007, Developmental biology.

[26]  E. Cooper.  Why developmental and comparative immunology , 1977 .

[27]  E. Myers,et al.  Basic local alignment search tool. , 1990, Journal of molecular biology.

[28]  T. Bosch,et al.  Growth regulation in Hydra: relationship between epithelial cell cycle length and growth rate. , 1984, Developmental biology.

[29]  Rodrigo Lopez,et al.  Multiple sequence alignment with the Clustal series of programs , 2003, Nucleic Acids Res..

[30]  F. Ausubel.  Are innate immune signaling pathways in plants and animals conserved? , 2005, Nature Immunology.

[31]  S. Brunak,et al.  Improved prediction of signal peptides: SignalP 3.0. , 2004, Journal of molecular biology.

[32]  M. Zasloff.  Antimicrobial peptides of multicellular organisms , 2002, Nature.

[33]  D. Schwartz,et al.  Specificity and Complexity of the Caenorhabditis elegans Innate Immune Response , 2007, Molecular and Cellular Biology.

[34]  J. Hoffmann,et al.  The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections , 2007, Nature Reviews Immunology.

[35]  T. Bosch,et al.  The evolution of immunity: a low-life perspective. , 2007, Trends in immunology.

[36]  James E. Evans,et al.  Molecular identification of a danger signal that alerts the immune system to dying cells , 2003, Nature.

[37]  A. Mescher,et al.  Regeneration or scarring: An immunologic perspective , 2003, Developmental dynamics : an official publication of the American Association of Anatomists.

[38]  F. Martinon,et al.  Gout-associated uric acid crystals activate the NALP3 inflammasome , 2006, Nature.

[39]  David J. Miller,et al.  The innate immune repertoire in Cnidaria - ancestral complexity and stochastic gene loss , 2007, Genome Biology.

[40]  M. Ashburner,et al.  Gene Ontology: tool for the unification of biology , 2000, Nature Genetics.

[41]  B. Lemaître,et al.  The host defense of Drosophila melanogaster. , 2007, Annual review of immunology.

[42]  J. Schröder,et al.  RNase 7, a Novel Innate Immune Defense Antimicrobial Protein of Healthy Human Skin* , 2002, The Journal of Biological Chemistry.

[43]  B. Beutler.  Innate immunity: an overview. , 2004, Molecular immunology.

[44]  Yun-Fai Chris Lau,et al.  [20] Suppression subtractive hybridization: A versatile method for identifying differentially expressed genes , 1999 .

[45]  T. Bosch,et al.  Discovery of genes expressed in Hydra embryogenesis. , 2006, Developmental biology.

[46]  T. Bosch,et al.  Enhanced antibacterial activity in Hydra polyps lacking nerve cells. , 2003, Developmental and comparative immunology.

[47]  C. David,et al.  Identification of caspases and apoptosis in the simple metazoan Hydra , 1999, Current Biology.

[48]  S. Gronow,et al.  Physicochemical characterization of carboxymethyl lipid A derivatives in relation to biological activity , 2005, The FEBS journal.

[49]  David J. Miller,et al.  Maintenance of ancestral complexity and non-metazoan genes in two basal cnidarians. , 2005, Trends in genetics : TIG.