Sea Urchins’ Unexpectedly
Diverse Immune Capability Raises Possibility That ‘Innate’ System May Also
Adapt In Vertebrates
Evolutionary ‘surprise’ could offer alternative immune therapy pathway
BETHESDA, Md. (Nov. 29, 2005) – 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.”
Source and funding
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 performed by Sham V. Nair, Heather Del Valle, David P.
Terwilliger and L. Courtney Smith at the Department of Biological Sciences,
George Washington University, Washington D.C.; and Paul S. Gross, Department
of Biochemistry, Medical University of South Carolina, Charleston. Nair is
now at the Department of Biological Sciences, Macquarie University, North
Ryde, NSW, Australia.
Research was supported by the National Science Foundation
(Smith and Gross).
Editor’s note: The media may obtain an
electronic copy of Nair et al. by contacting Donna Krupa at the American
Physiological Society, (301) 634-7209, cell (703) 967-2751 or
dkrupa@the-aps.org.
* * *
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