Auburn University scientists make breakthrough discovery on the evolution of the innate immune system

The laboratory of Kenneth Halanych, the Schneller Endowed Chair in the Department of Biological Sciences at Auburn University, has made a discovery that could have widespread implications for how scientists study the function of the human immune system. Led by doctoral student Michael Tassia, the team’s research revealed that humans and their closest invertebrate relatives share core components of their innate immune systems, components that date back more than 500 million years.

“Humans belong to a group called ‘Deuterostomes’ that include vertebrate animals as well as invertebrate animals like sea stars, sea urchins, sea squirts and acorn worms,” said Tassia.

“All of these groups had gill slits, much like fish, early in their history,” added Halanych.

Tassia and the team in the Halanych lab studied genetic datasets of more than 40 different deuterostome species including human and invertebrate. The research showed evidence that humans and other deuterostomes share a common evolutionary history of their innate immune systems.

“Humans and other vertebrates possess two types of immune systems–innate and adaptive,” said Tassia. “The adaptive immune system is the one we are more familiar with. It contains components such as antibodies that allow for ‘immunological memory,’ which is why immunizations are an effective tool against diseases and pathogens. Whereas the adaptive immune system must ‘learn’ to recognize a pathogen, the innate immune system is prepared from the get-go. The innate immune system relies on a suite of molecules called ‘pattern-recognition receptors’ which, over long periods of evolution, have adapted to recognize common molecular patterns associated with bacteria, fungi and viruses. So, if bacteria like E. coli get into somewhere they shouldn’t, such as a really nasty paper cut, cells in your body sporting these pattern-recognition receptors are ready to mount a rapid immune response, causing inflammation, recruiting more immune cells and destroying those bacteria.”

Tassia explained that the adaptive immune system is exclusive to vertebrates. Components of the innate immune system, on the other hand, predate vertebrates and are present in groups as old as jellies, whose last common ancestor with vertebrates existed more than 500 million years ago. As a result, he began his work by comparing the most well-known pattern-recognition receptors, “Toll-like receptors,” or TLRs, from more than 40 different invertebrate and vertebrate species.

“In our research, we looked at the much bigger system, starting with the diversity of TLRs in each of our species and continuing further by examining whether or not all the other important components required for the system to work are present across deuterostomes,” said Tassia. “Our findings indicate that nearly all the components are present across all the major deuterostome groups, suggesting their innate immune system was present in the last common ancestor more than 500 million years ago and was expanded upon in vertebrates and other groups. Our study also used phylogenetic methods to evaluate the similarity of TLRs between major animal lineages. Interestingly, we were able to identify a group of TLRs very closely related to a mammalian TLR that is critical for recognizing viruses, suggesting this particular method for antiviral defense may be more evolutionarily ancient than previously expected and could predate the origin of vertebrates.”

The realization that the innate immune system of vertebrates and their close invertebrate relatives is similar opens the door to developing more controllable laboratory experiments to understand immune system evolution.

“Often the generation time and ability to keep invertebrates in the laboratory can make them logistically favorable for studying vertebrate systems,” said Halanych.

The research findings are the result of years of study, beginning with Halanych’s dissertation and long-standing interest in the evolution of hemichordates and echinoderms–marine invertebrates–and continuing with the work of doctoral students in the Halanych lab, as well as publically available information from the National Institutes of Health. Tassia gathered several terabytes of genetic data from the previous research efforts and spent approximately two years developing a bioinformatic, computational framework that allowed him to confidently identify and perform analysis on specific genes.

“This work is a great example of how bioinformatics tools can help answer important questions of organismal biology,” said Halanych. “The Tassia et al. paper has helped push the laboratory, and Auburn University, further into the forefront of marine invertebrate genomics.”

The research results were published in the prestigious scientific journal, Proceedings of the National Academy of Sciences, or PNAS, in a paper titled, “Toll-like receptor pathway evolution in deuterostomes”.

PNAS is one of the top scientific journals and is run by the National Academy of Sciences, an association of the world’s top scientists across many disciplines. Intellectual and scientific standards for the journal are very high, signifying that work published in PNAS is likely to have a significant impact on the field of study.