How to Explore the Path They Went Why Cnidarians Matter

A few years ago, outside the vertebrates the molecular nature of immune reactions could be approached only in a very few "model" species. Now the tide has turned: in silico approaches allow us to mine practically any species of choice. The question is no longer can we molecularly study this species or not. The question now is does this species tell us anything new about the history of the immune system which we did not know before and which we can learn from hardly anywhere else. In this respect, comparative immunology entered an era of radically widening horizons. As a sister group to the bilateria, Cnidaria are an important phylum, potentially providing key insight to the ancestry and evolution of immune reactions. As outlined above and elsewhere (Hemmrich et al. 2007; Miller et al. 2007), much effort in cnidarian research has recently been directed towards cloning evolutionarily conserved genes known to play critical roles in innate immunity in bilaterians. Data from several cnidarian taxa indicate convincingly that successful strategies for the detection and elimination of pathogens are present at that level of animal evolution. In the absence of an adaptive immune system, cnidarians employ an elaborate innate immune system to detect and eliminate nonself and to disarm microbial attackers. Beside an impressive accumulation of gene sequences, several novel tools and the development of genomic resources including the availability of trans-genic Hydra (Wittlieb et al. 2006) have brought a new perspective on innate immunity in cnidarians and now pave the way for many important scientific and technological applications. Cnidaria emerge as kind of opener of discussions, an invitation to think about the structures and mechanisms of immune defense and self/nonself recognition.

To understand why Cnidaria matter, we must appreciate their flexibility and fathomless versatility of defense reactions that have helped them to survive for so long. As outlined above, there is no problem in innate immunity - intraspecies competition, cell lineage competition, host/pathogen and host/symbiont interactions - the cnidarians did not attempt to solve. Thus, whatever we experience with our own innate immune system, whatever we hope to learn, we see that the cnidarians have been there before us. There is a second reason why innate immune reactions in cnidarians matter: Cnidaria may emerge as attractive model systems to understand human barrier disorders by describing ancient mechanisms of host/microbial interactions and the resulting evolutionary selection processes or advantages. The identification of genes responsible for human diseases affecting biological barriers (e.g., skin or intestinal mucosa) often does not in itself provide a clue to etiopatho-genesis or therapeutic targets, as the interaction of a suite of genes in a complex system such as the human is difficult to understand. Likewise the involved pathways that ultimately lead to the development of the disease phenotype are unclear. Searching for the evolutionary origin of the disease-causing genes and characterizing the variation in such genes under known evolutionary pressures may provide insights into the development of diseases in humans and identify new targets for therapy or prevention. Cnidaria may allow to unravel the complex interplay of host/pathogen signaling cascades that are also relevant to human barrier organs and its microbiota. Finally, in human medicine, the increasing prevalence of antibiotic-resistant microbes requires the development of new antimicrobials. Antimicrobial peptides of animal origin may be an effective alternative or additive of conventional antibiotics for therapeutic use. The recent identification of highly active antimicrobial peptides in hydra and jellyfish show that antimicrobial pep-tides from marine and freshwater cnidarians may represent a largely unexploited resource that can afford the design of new antibiotics with broad-spectrum antimicrobial activity.

Acknowledgement Supported by grants from the Deutsche Forschungsgemeinschaft (SFB 617).

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