News Release: Research, School of Medicine
May 20, 2009
Adaptive Immunity Linked to Lifespan Genes in C. Elegans
Caenorhabditis elegans. Download larger image (168 K)."Vaccinating" roundworms can teach humans about connections between immunity, longevity and the nervous system, scientists say.
Even though the roundworm C. elegans doesn't make antibodies like animals do, worms can be "immunized" by exposure to pathogenic bacteria, Emory researchers have found. The results are published in the May issue of the journal Cell Host & Microbe.
Briefly exposing worms to enteropathogenic E. coli (EPEC), bacteria that give humans severe diarrhea, allows them to survive a later exposure that would otherwise be lethal.
"In a basic way, this is like vaccinating people against a bacteria or virus, so that if they encounter it again, they are able to survive," says Daniel Kalman, PhD, assistant professor of pathology and infectious diseases, Emory University School of Medicine. "We figured out that the same thing can be done with the worms' ancient immune system, and that this requires innate immunity and aging factors, which are highly conserved from worms to humans."
Not all strains of bacteria make worms tougher. The paralyzing toxins EPEC secretes and some other "contact-dependent" part of the bacteria are important for the conditioning process, but the worms can distinguish "good from bad" bacteria, says Kalman.
By testing mutant worms' ability to survive in greater numbers after exposure to bacteria, Kalman and postdoctoral fellow Akwasi Anyanful found the conditioning process requires a gene involved in worms' response to insulin called daf-16. Daf-16 is also involved in helping worms resist stresses like starvation or heat.
Previous research on C. elegans has uncovered links between insulin-response genes (which resemble insulin-response genes in humans) and whether a worm has a long or short lifespan. The gene daf-16 must be intact for mutations in other genes that extend a worm's lifespan to have their effects.
"In a way, this makes sense, because when roundworms die, many of them probably die of a bacterial infection," Kalman says. "Our discovery sets up the ability to study the genes involved, and the connections between exposure to pathogens, the adaptive immune response and lifespan, in greater detail."
The conditioning also requires a specific group of nerve cells that use the chemical messenger dopamine, the authors found.
The research was supported by the National Institutes of Health.
Reference:
Anyanful, A., Easley, K.A., Benian, G.M. and Kalman D. "Conditioning protects C. elegans from lethal effects of a pathogen through activation of genes that regulate lifespan and innate immunity." Cell Host & Microbe, 5, 450-462 (2009).
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