Social amoeba shows ancient origins of immunity
By Ruth SoRelle, M.P.H.
When Adam Kuspa, Ph.D., chair of biochemistry and molecular biology at Baylor College of Medicine, found 'sentinel' cells in the social amoeba (Dictyostelium discoideum), he not only had a clue as to how old immunity is in evolutionary terms, but also one as to what is needed for an organism to become multicellular. His report appeared in a recent issue of the journal Science.
Stress triggers changes in single-celled organisms
Dictyostelium discoideum is unusual. Commonly, it exists as a single cell. However, stress, such as starvation, forces these individual cells to coalesce into a multi-cellular slug that moves. Eventually the slug produces cells that perform specific functions – spores and stalks. In other words, the cells differentiate and take on specific functions in this new organism.
In his report in Science, Kuspa and his colleagues describe a new kind of cell they identify in the organism. They dubbed it a 'sentinel' cell to indicate its function.
Sentinel cells circulate within the slug, engulfing invading bacteria and sequestering poisons or toxins, eventually eliminating these from the slug. These cells often operate through a particular mechanism in the cells controlled by a Toll/Interleukin-1 Receptor domain protein (TirA), Kuspa and his team found.
Amoeba one of four multicellular life forms
This signaling pathway or a very similar one is present in plants and animals, he said. Now it has been identified in amoeba. It has not been found in fungi.
"Amoeba have, in the last 10 years, become appreciated as one of the four main forms of life in the crown group of eukaryotic (multicellular) organisms – plants, animals, fungi and amoeba," said Kuspa. "What allowed them to become multicellular?"
One way to estimate the characteristics of the organism that went before those that were multicellular is to look for characteristics that are present in two, three or all four of these main groups, he said.
"Those were likely present in the progenitor organism," said Kuspa. Because three of the four major groups of organisms have this pathway, "I argue that means that the progenitor of all multicellular organisms had this pathway. Since that organism was not likely multicellular, it must have used it as some kind of signaling to respond to bacteria in the environment."
Ability to distinguish self is key
Looking at it from another point of view, "it's possible that one of the properties of those (crown) organisms that allowed them to become multicellular was the ability to distinguish self from non-self – the hallmark of an immune system," said Kuspa. "The speculation is that a requirement of multicellularity is that you develop systems to recognize pathogens and other non-self cells from yourself."
Kuspa sees two paths for future research in the area. One is to look for evidence of the same immune mechanism and protein in other kinds of amoeba. The other is to look at unicellular organisms to determine if they have this same kind of immune signaling pathway.
"If none of the early diverging organisms that never became multicellular developed this kind of signaling system, it would subtly strengthen our argument," he said.
Others who took part in this work include Drs. Guokai Chen and Olga Zhuchenko, both of BCM.
Funding for this work came from the National Institutes of Health. The article can be found at http://www.sciencemag.org/cgi/content/full/317/5838/678.


