Sea urchins’ unexpectedly diverse ’innate’ immune capability points to new research avenue

’We are beginning to understand how an animal without an adaptive immune system can still protect itself,’ Smith said, adding: ’The sea urchin may use genes that are different from antibodies and possibly even different mechanisms from humans.’

Inside that seemingly docile sea urchin there’s a surprisingly active innate immune system, probably utilizing previously unrecognized immune mechanisms, that may also actively function in vertebrates, including humans, according to researchers at George Washington University, in Washington, D.C.

“Discovering this capability goes completely against the long-accepted paradigm that the innate immune system which had evolved over a long period of time was ’perfect’ in terms of meeting lower animals’ needs,” L. Courtney Smith, associate professor of Biological Sciences, said. “It was a big surprise, that continues to astound us,” she added.

Like many “lower” animals such as insects, earth worms and others without an adaptive immune system (one that can make antibodies), a sea urchin’s innate system seems to produce a wide diversity of proteins that probably can attack germs and protect the sea urchin from infection, a new study from Smith’s lab shows.

She and her colleagues studied the purple sea urchin’s response to a standard bacterial insult (a fragment of the cell wall called lipopolysaccharide, or LPS) using a genomic screen. They discovered that the sea urchin produces a surprisingly large number of proteins against LPS, and that many of them are similar but also show an unexpected amount of variability.

Possible role of ’innate immunity’ higher up the evolutionary ladder

“We are beginning to understand how an animal without an adaptive immune system can still protect itself,” Smith said, adding: “We’re beginning to appreciate that the sea urchin may use genes that are different from antibodies and possibly even different mechanisms from humans and yet is still able to produce an array of proteins with lots of diversity.”

The paper, “Macroarray analysis of coelomocyte gene expression in response to LPS in the sea urchin. Identification of unexpected immune diversity in an invertebrate,” appears in Physiological Genomics, published by the American Physiological Society. Research was by Sham V. Nair, Heather Del Valle, David P. Terwilliger and L. Courtney Smith at George Washington University; and Paul S. Gross at Medical University of South Carolina.

The paper concludes: “Identification of novel mechanisms for generating immune diversity in invertebrates, which has implications for innate immune capabilities in all animals, may result in a better understanding of innate immunity in higher vertebrates.”

Latest technology aimed at the base of animal phylogeny branch that includes humans

Sea urchins are at the very bottom of the same branch of the evolutionary tree with sharks (where a type of adaptive immune system was first identified) and the rest of the vertebrates, which include fish, reptiles, birds and of course, mammals such as humans. Thus further understanding of the sea urchin’s immune mechanism could open research possibilities in several directions.

To understand the sea urchin immune system, Smith said her lab “employed comparative and phylogenetic approaches to analyze the sea urchin protein sequences, which yield information on the evolution of immunity in the deuterostome lineage of animals,” the subject of the current paper. Another line of investigation is working on characterizing “a large set of putative antimicrobial proteins induced by challenge” with LPS. Using proteomics, genomics and molecular biology, the lab is “working to understand the functions of these proteins, the number of genes in the sea urchin genome and the mechanisms for generating this high level of diversity in an invertebrate immune response,” in this case, to LPS.

New mechanisms believed at work to produce diverse immune response

Smith said they had identified a particularly large group of “similar but diverse” proteins that appeared after LPS injection, “which we propose represent a major player in the immune response of the sea urchin.” The family of transcripts had previously been designated as 185/333. The paper in Physiological Genomics “is the first report on a genomic screen showing sequences that are similar enough to look like they’re coming from the same gene,” Smith noted, but they don’t. This is a current research effort in Smith’s lab.

Nevertheless, she added, the results seem to indicate how invertebrates cope so successfully in their pathogenic environment, perhaps using as yet undiscovered mechanisms, which may also exist in immune systems of more advanced animals. “Our preliminary results indicate there are too few genes to explain the observed nucleotide variability in the ETSs (expressed sequence tags),” the paper said. “This suggests that there may be mechanisms for generating sequence diversity in the 185/333 transcripts that have not been previously characterized.”

“This was the big surprise in our findings,” Smith noted. “”It is evolutionary significant that animals other than vertebrates have mechanisms, most still unknown, to diversify their innate immune system to address the problem of microbes always finding new ways to infect. It turns out that we and other vertebrates aren’t unique in that. Probably all animals and plants to do this, but we never even thought of asking that question before,” she said.

Next steps that could ’revolutionize’ paradigm on invertebrate immune function

The paper itself summarizes the findings and implications like this: “The diversity shown in the innate immune responses of the sea urchin, snail, shrimp and the Amphioxus responding to bacterial, parasitic, fungal, and viral challenges suggests that these animals, and perhaps most animals, may have hitherto unrecognized mechanisms to diversify their responses to foreignness. These mechanisms may either result in broad protection against pathogens or in directed expression of specific peptides to combat specific infecting microbes. The analysis of the sea urchin system promises to uncover mechanisms that generate diversity in immune response, the results of which will contribute to a paradigm shift in our understanding of invertebrate immunity, as suggested by (Martin F.) Flajnik and (Louis) du Pasquier.”

Smith added: “A series of followup experiments of the sea urchin’s immune system are expected to revolutionize our understanding of the evolution of immunity and will change completely the current paradigm of how invertebrate immune systems function.”